)| PMID |
12654515 ( ) |
|---|---|
| Title | VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death. |
| Abstract | The increased oxidative stress induced by mutant SOD1 is associated with motor neuron degeneration in both human ALS and transgenic mice expressing mutant SOD1. Vascular endothelial growth factor (VEGF) is neurotrophic and also protects from hypoxia-induced neuronal injury. The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined using a mouse NSC34 motor neuron-like cell culture system. Infection with adenovirus containing mutant G93A-SOD1, but not vector control or wild-type SOD1, increased cellular oxidative stress and motor neuron-like cell death. However, NSC34 cells pretreated with VEGF displayed a dose-dependent resistance to oxidative damage from hydrogen peroxide, TNF-alpha, and mutant G93A-SOD1. VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells. Pharmacological inhibitors and constitutively active as well as dominant negative mutants of MAPK and PI3-K revealed that the protective effects of VEGF were mediated via the PI3-K activity, and that MAPK activation was not associated with NSC34 cell survival. Furthermore, VEGF-induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in the presence of mutant G93A-SOD1. Thus, VEGF protected mouse NSC34 motor neuron-like cell death from mutant G93A-SOD1 effects via PI3-K/Akt activation. 46285, USA. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 12680 | VEGFA | vascular endothelial growth factor A | 86 | VEGF-associated | VEGF-induced | vascular endothelial growth factor | VEGF-mediated | vascular permeability factor | VEGF-stimulated | VEGF-treated | |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | 42 | pi3 kinase | PI3-K | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 35 | SOD1 | SOD1-infected | SOD1-mediated | SOD1-induced | mSOD1 | superoxide dismutase | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 33 | Akt | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 29 | ERK | MAPK-related | MAP | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 7 | TNF-A | |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | 5 | ERK1 | Erk1 | |
| 8979 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | 4 | p85 | P85 | |
| 6840 | MAP2K1 | mitogen-activated protein kinase kinase 1 | 4 | MEK1 | |
| 16860 | SART3 | squamous cell carcinoma antigen recognized by T cells 3 | 3 | p110 | P110 | |
| 8975 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | 2 | phosphatidylinositol 3 kinase | |
| 1706 | CD8A | CD8a molecule | 1 | p32 | |
| 3763 | FLT1 | fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor) | 1 | Flt-1 | |
| 727 | ARTN | artemin | 1 | neurotrophic factor | |
| 1516 | CAT | catalase | 1 | catalase | |
| 6307 | KDR | kinase insert domain receptor (a type III receptor tyrosine kinase) | 1 | Flk-1 | |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | 1 | caspase 9 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | The increased oxidative stress induced by mutant SOD1 is associated with motor neuron degeneration in both human ALS |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | degeneration in both human ALS and transgenic mice expressing mutant SOD1 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Vascular endothelial growth factor (VEGF) VEGF is neurotrophic and also protects from hypoxia-induced neuronal injury |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined using a mouse NSC34 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | adenovirus containing mutant G93A-SOD1 but not vector control or wild-type SOD1 increased cellular oxidative stress and motor neuron-like cell death |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | However NSC34 cells pretreated with VEGF displayed a dose-dependent resistance to oxidative damage from hydrogen peroxide |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | displayed a dose-dependent resistance to oxidative damage from hydrogen peroxide TNF-_amp_#x3b1 and mutant G93A-SOD1 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | and constitutively active as well as dominant negative mutants of MAPK and PI3-K revealed that the protective effects of VEGF were |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | active as well as dominant negative mutants of MAPK and PI3-K revealed that the protective effects of VEGF were mediated via |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | of MAPK and PI3-K revealed that the protective effects of VEGF were mediated via the PI3-K activity and that MAPK activation |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | that the protective effects of VEGF were mediated via the PI3-K activity and that MAPK activation was not associated with NSC34 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | of VEGF were mediated via the PI3-K activity and that MAPK activation was not associated with NSC34 cell survival |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-induced | 3.8 | Furthermore VEGF-induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.1 | Furthermore VEGF-induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in the presence |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Thus VEGF protected mouse NSC34 motor neuron-like cell death from mutant G93A-SOD1 |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | motor neuron-like cell death from mutant G93A-SOD1 effects via PI3-K/Akt PI3-K Akt activation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | neuron-like cell death from mutant G93A-SOD1 effects via PI3-K/Akt PI3-K Akt activation |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | discovery that mutations of the copper_amp_#x2013 zinc superoxide dismutase (SOD1) SOD1 gene cause a portion of human familial ALS and that |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | human familial ALS and that transgenic animal models expressing mutant SOD1 mimic human ALS have contributed significantly to our understanding of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | The G93A mutation in SOD1 (G93A-SOD1) G93A-SOD1 is one of the 90 currently known mutations |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | Nevertheless effective approaches to prevent mutant SOD1-mediated motor neuron death remain largely unidentified |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Recently vascular endothelial growth factor (VEGF) VEGF has been demonstrated to have neurotrophic effects by promoting neuronal |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Knockout mice with deleted hypoxic response elements in the VEGF promoter region develop a motor neuron-like disease mimicking human ALS |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | motor neuron-like disease mimicking human ALS 40 suggesting that hypoxia-mediated VEGF expression may be associated with motor neuron degeneration |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF also known as vascular permeability factor is a dimeric glycoprotein |
| 3763 | FLT1 | fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor) | Flt-1 | 0.6 | binds to endothelial cell specific receptors fms-like tyrosine kinase (Flt-1) Flt-1 and fetal liver kinase (Flk-1) Flk-1 16 and 36 |
| 6307 | KDR | kinase insert domain receptor (a type III receptor tyrosine kinase) | Flk-1 | 0.3 | fms-like tyrosine kinase (Flt-1) Flt-1 and fetal liver kinase (Flk-1) Flk-1 16 and 36 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Acting through these receptors VEGF is believed to initiate several intracellular signal transduction systems including |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | initiate several intracellular signal transduction systems including phosphatidylinositol 3-kinase (PI3-K) PI3-K and mitogen-activated protein kinase (MAPK) MAPK 42 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | including phosphatidylinositol 3-kinase (PI3-K) PI3-K and mitogen-activated protein kinase (MAPK) MAPK 42 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Hypoxia and spinal cord injury have been demonstrated to increase VEGF expression 19 20 and 35 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Neuronal or neuronal-like cells pretreated with VEGF prevent glutamate- and hypoxia/ischemia-mediated hypoxia ischemia-mediated cell death in vitro |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | More importantly topical application of VEGF reduces ischemia-mediated brain damage in vivo 19 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Although some studies have focused on the effects of VEGF on the central nervous system (CNS), CNS the potential role |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | the central nervous system (CNS), CNS the potential role of VEGF in motor neuron survival by mutant SOD1 effects remains largely |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | potential role of VEGF in motor neuron survival by mutant SOD1 effects remains largely unknown |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | the NSC34 motor neuron-like cell culture model to test whether VEGF can prevent mutant SOD1-mediated motor neuron degeneration |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | cell culture model to test whether VEGF can prevent mutant SOD1-mediated motor neuron degeneration |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | causes severe disease onset and progression was used to analyze VEGF effects on motor neuron degeneration |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | We demonstrate that NSC34 cells pretreated with VEGF reduces mutant G93A-SOD1- TNF-_amp_#x3b1;- and hydrogen peroxide-mediated motor neuron-like cell |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF activates both PI3-K and MAPK activities in NSC34 motor neuron-like |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF activates both PI3-K and MAPK activities in NSC34 motor neuron-like cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF activates both PI3-K and MAPK activities in NSC34 motor neuron-like cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | pharmacological inhibitors and constitutively active and dominant negative mutants of MAPK and PI3-K we further demonstrate that PI3-K activity but not |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | and constitutively active and dominant negative mutants of MAPK and PI3-K we further demonstrate that PI3-K activity but not MAPK activity |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | negative mutants of MAPK and PI3-K we further demonstrate that PI3-K activity but not MAPK activity protects mouse NSC34 cells from |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | and PI3-K we further demonstrate that PI3-K activity but not MAPK activity protects mouse NSC34 cells from mutant G93A-SOD1 effects |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | In addition we show that Akt activation promotes NSC34 motor neuron-like cell survival in the presence |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Thus we propose that the neurotrophic-like activity of VEGF on mouse NSC34 motor neuron-like cell survival is mediated by |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | neuron-like cell survival is mediated by activation of the PI3-K/Akt PI3-K Akt pathway 2 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | cell survival is mediated by activation of the PI3-K/Akt PI3-K Akt pathway 2 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF was purchased from Calbiochem (San San Diego CA USA |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | TNF-_amp_#x3b1 N -acetyl-cysteine (N-AC), N-AC 5_amp_#x2032 5_amp_#x2032 -dimethylpryrroline-N -oxide (DMPO), DMPO |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | Polyclonal antibody against SOD1 was purchased from Chemicon International (Temecula, Temecula CA USA |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | Wild-type and constitutively active PI3-K catalytic subunit p110 (myristoylated) myristoylated and dominant negative PI3-K regulatory |
| 16860 | SART3 | squamous cell carcinoma antigen recognized by T cells 3 | p110 | 1.3 | Wild-type and constitutively active PI3-K catalytic subunit p110 (myristoylated) myristoylated and dominant negative PI3-K regulatory subunit p85 were |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | active PI3-K catalytic subunit p110 (myristoylated) myristoylated and dominant negative PI3-K regulatory subunit p85 were purchased from Upstate Biochemical (Lake Lake |
| 8979 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | p85 | 0.6 | subunit p110 (myristoylated) myristoylated and dominant negative PI3-K regulatory subunit p85 were purchased from Upstate Biochemical (Lake Lake Placid NY USA |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Constitutively active (myristoylated) myristoylated and dominant negative Akt (K179M-Akt) K179M-Akt were kindly provided by Dr Alfonso Bellacosa Fox |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Mouse NSC34 cells were pretreated with VEGF for 30 min and then infected with 2_amp_#xd7 10 6 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | with complete medium either in the presence or absence of VEGF for various lengths of time before analysis 32 2.5 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 2.2 | MAP kinase activation assay |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 2.2 | MAP kinase activation was measured by the phosphorylation of ERK1/2 ERK1 |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 2.7 | MAP kinase activation was measured by the phosphorylation of ERK1/2 ERK1 2 using anti-phospho-ERK1/2 anti-phospho-ERK1 2 antibody (Cell Cell Signaling |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-stimulated | 3.8 | Briefly control and VEGF-stimulated NSC34 cells were washed twice with ice-cold PBS and lysed |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 2.2 | membrane and probed with anti-phospho-ERK1/2 anti-phospho-ERK1 2 antibody that recognizes ERK only when it is phosphorylated at Thr202 and Tyr204 (Cell |
| 8979 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | p85 | 0.6 | Cell lysates were immunoprecipitated with p85 antibody and were subsequently used for PI3-K activity assay |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | were immunoprecipitated with p85 antibody and were subsequently used for PI3-K activity assay |
| 1706 | CD8A | CD8a molecule | p32 | 0.3 | kinase reaction was initiated by adding 10 _amp_#x3bc Ci of p32 ATP (6000 6000 Ci/mmol, Ci mmol DuPont-NEN Boston MA USA |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Akt activation assay |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Akt activation was examined by Western blotting with phosphorylation specific Akt |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Akt activation was examined by Western blotting with phosphorylation specific Akt antibody (Cell Cell Signaling |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-treated | 3.8 | expressed as mean_amp_#xb1 S.E.M and the differences between vehicle- and VEGF-treated mouse NSC34 motor neuron-like cells were analyzed using two-tailed Student |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | oxidative stress appears to be an early event of mutant SOD1-mediated motor neuron degeneration although the causal relationships between mutant SOD1-mediated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | SOD1-mediated motor neuron degeneration although the causal relationships between mutant SOD1-mediated oxidative stress and mutant SOD1-mediated motor neuron death are not |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | the causal relationships between mutant SOD1-mediated oxidative stress and mutant SOD1-mediated motor neuron death are not fully elucidated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | Infection with adenovirus containing human wild-type SOD1 (WT-SOD1) WT-SOD1 and human mutant G93A-SOD1 (G93A-SOD1) G93A-SOD1 increased target |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | neuron-like cell death similar to that of hydrogen peroxide and TNF-_amp_#x3b1 ( Fig 1D 3.2 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF protects from mutant SOD1- TNF-_amp_#x3b1;- and H 2 O 2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 1.7 | VEGF protects from mutant SOD1- TNF-_amp_#x3b1;- and H 2 O 2 -mediated mouse NSC34 motor |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF and vehicle pretreated mouse NSC34 cells were infected with adenovirus |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | were infected with adenovirus containing mutant G93A-SOD1 and exposed to TNF-_amp_#x3b1 and hydrogen peroxide respectively |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF treatment was associated with significant increases in cell survival in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | with significant increases in cell survival in the presence of mSOD1 TNF-_amp_#x3b1 and hydrogen peroxide ( Fig 2 3.3 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | significant increases in cell survival in the presence of mSOD1 TNF-_amp_#x3b1 and hydrogen peroxide ( Fig 2 3.3 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF transiently activates PI3-K and MAPK activities |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF transiently activates PI3-K and MAPK activities |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF transiently activates PI3-K and MAPK activities |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | PI3-K and/or and or MAPK signaling pathways underlie critical components of |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | PI3-K and/or and or MAPK signaling pathways underlie critical components of the survival-related activity of |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Thus we tested whether VEGF regulates PI3-K and/or and or MAPK activation in NSC34 cells |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | Thus we tested whether VEGF regulates PI3-K and/or and or MAPK activation in NSC34 cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | Thus we tested whether VEGF regulates PI3-K and/or and or MAPK activation in NSC34 cells |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF induced concentration- and time-dependent increases in PI3-K and MAPK activities |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF induced concentration- and time-dependent increases in PI3-K and MAPK activities ( Fig 3 and Fig 4 suggesting |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF induced concentration- and time-dependent increases in PI3-K and MAPK activities ( Fig 3 and Fig 4 suggesting that these |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-associated | 3.8 | and Fig 4 suggesting that these pathways may potentially mediate VEGF-associated motor neuron-like cell protection 3.4 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-mediated | 3.8 | VEGF-mediated PI3-K activity not MAPK activity promotes mouse NSC34 motor neuron-like |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF-mediated PI3-K activity not MAPK activity promotes mouse NSC34 motor neuron-like cell |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF-mediated PI3-K activity not MAPK activity promotes mouse NSC34 motor neuron-like cell survival in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | NSC34 motor neuron-like cell survival in the presence of mutant SOD1 |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | To further examine the respective contributions of the PI3-K and MAPK signaling pathways to VEGF-induced cell survival the PI3-K |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | To further examine the respective contributions of the PI3-K and MAPK signaling pathways to VEGF-induced cell survival the PI3-K inhibitors LY294002 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF-induced | 3.8 | respective contributions of the PI3-K and MAPK signaling pathways to VEGF-induced cell survival the PI3-K inhibitors LY294002 at 50 _amp_#x3bc M |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | PI3-K and MAPK signaling pathways to VEGF-induced cell survival the PI3-K inhibitors LY294002 at 50 _amp_#x3bc M or Wortmannin at 20 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | at 20 _amp_#x3bc M (data data not shown and the MAPK inhibitor PD98059 at 20 _amp_#x3bc M were administered to the |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | PI3-K blockers reduced NSC34 cell viability even in the presence of |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | blockers reduced NSC34 cell viability even in the presence of VEGF ( Fig 5A while PD98059 did not modify cell survival |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | In addition transfection with the constitutively active catalytic subunit of PI3-K P110 but not with the constitutively active MEK1 the upstream |
| 16860 | SART3 | squamous cell carcinoma antigen recognized by T cells 3 | P110 | 1.3 | addition transfection with the constitutively active catalytic subunit of PI3-K P110 but not with the constitutively active MEK1 the upstream activating |
| 6840 | MAP2K1 | mitogen-activated protein kinase kinase 1 | MEK1 | 2.2 | subunit of PI3-K P110 but not with the constitutively active MEK1 the upstream activating kinase of ERK prevented mutant G93A-SOD1-mediated NSC34 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 2.2 | with the constitutively active MEK1 the upstream activating kinase of ERK prevented mutant G93A-SOD1-mediated NSC34 cell death ( Fig 5B |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | Conversely transfections with the dominant negative regulatory subunit of PI3-K P85 promoted cell death even in the presence of VEGF |
| 8979 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | P85 | 0.6 | Conversely transfections with the dominant negative regulatory subunit of PI3-K P85 promoted cell death even in the presence of VEGF while |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | PI3-K P85 promoted cell death even in the presence of VEGF while transfection with dominant negative MEK1 was void of any |
| 6840 | MAP2K1 | mitogen-activated protein kinase kinase 1 | MEK1 | 2.2 | in the presence of VEGF while transfection with dominant negative MEK1 was void of any effect on NSC34 cell viability after |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Activation of Akt by VEGF contributes to the protection from mutant SOD1-mediated motor neuron-like cell |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | of Akt by VEGF contributes to the protection from mutant SOD1-mediated motor neuron-like cell death |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.1 | Activation of Akt by VEGF contributes to the protection from mutant SOD1-mediated motor |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | One of the downstream effectors of PI3-K is Akt activation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.1 | One of the downstream effectors of PI3-K is Akt activation |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | We therefore initially examined whether VEGF treatment of NSC34 cells was associated with Akt phosphorylation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | examined whether VEGF treatment of NSC34 cells was associated with Akt phosphorylation |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Indeed cells exposed to VEGF displayed concentration- and time-dependent Akt activation ( Fig 5D and |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Indeed cells exposed to VEGF displayed concentration- and time-dependent Akt activation ( Fig 5D and E |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | resulted in a significant reduction in the protective effect by VEGF on survival of NSC34 cells infected with mutant G93A-SOD1 ( |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Overexpression of the dominant negative mutant of Akt resulted in a significant reduction in the protective effect by |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | In contrast expression of constitutively active Akt increased cell survival despite the presence of mutant G93A-SOD1 ( |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Taken together the data indicate that activation of Akt by VEGF contributes to the protection from NSC34 motor neuron-like cell death |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | NSC34 motor neuron-like cell death associated with expression of mutant SOD1 4 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.1 | Taken together the data indicate that activation of Akt by VEGF contributes to the protection from NSC34 motor neuron-like |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | In this study we show that VEGF administration significantly protects from the decreased cell viability induced by |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | We further demonstrate that the protective effects of VEGF are critically dependent on the activation of the PI3-K-Akt pathway |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | on the activation of the PI3-K-Akt pathway and independent of MAPK activation |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | lines of evidence prompted us to examine the effects of VEGF on mutant SOD1-mediated motor neuron-like cell death (i) i VEGF |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | prompted us to examine the effects of VEGF on mutant SOD1-mediated motor neuron-like cell death (i) i VEGF acts as a |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF on mutant SOD1-mediated motor neuron-like cell death (i) i VEGF acts as a neurotrophic factor preventing hypoxia (ischemia)-mediated ischemia -mediated |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | (iii) iii disruption of the hypoxic response elements in the VEGF promoter region of transgenic mice elicits a pattern of motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | in a mouse model 40 and (iv) iv mutations of SOD1 result in enhanced oxidative stress and contribute at least partially |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Thus one of the beneficial effects of VEGF on cell survival could theoretically be ascribed to a protective |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Our findings confirm such an hypothesis whereby VEGF is effective in preventing mutant SOD1-induced mouse NSC34 motor neuron-like |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-induced | 1.7 | such an hypothesis whereby VEGF is effective in preventing mutant SOD1-induced mouse NSC34 motor neuron-like cell death |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF was initially identified as an angiogenic factor that stimulates endothelial |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | More recently VEGF was shown to induce neuroprotective functions both in vitro and |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | For example VEGF rescues HN33 and hippocampal neuronal cells from the apoptosis induced |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Furthermore VEGF exerts direct neurotrophic effects on axonal outgrowth and neuronal survival |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Our current findings indicate that VEGF promotes motor neuron-like cell survival in the presence of mutant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | promotes motor neuron-like cell survival in the presence of mutant SOD1 thereby supporting the notion that deficits in VEGF protein induction |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | of mutant SOD1 thereby supporting the notion that deficits in VEGF protein induction or release may contribute to motor neuron degeneration |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | These results also suggest that VEGF may have beneficial therapeutic effects in the prevention of motor |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | It is well established that VEGF can activate both PI3-K and MAPK (MEK/ERK) MEK ERK pathways |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | It is well established that VEGF can activate both PI3-K and MAPK (MEK/ERK) MEK ERK pathways yet the protective effect |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | is well established that VEGF can activate both PI3-K and MAPK (MEK/ERK) MEK ERK pathways yet the protective effect of VEGF |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 2.2 | that VEGF can activate both PI3-K and MAPK (MEK/ERK) MEK ERK pathways yet the protective effect of VEGF on motor neuron-like |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | MAPK (MEK/ERK) MEK ERK pathways yet the protective effect of VEGF on motor neuron-like cell survival upon the expression of mutant |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | While the specific functional roles played by the MAPK pathway are unclear it is likely that this pathway may |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | of Matsuzaki et al 34 who showed that both the PI3-K and MAPK pathways participate in neuronal cell protection by VEGF |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | et al 34 who showed that both the PI3-K and MAPK pathways participate in neuronal cell protection by VEGF against glutamate |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | PI3-K and MAPK pathways participate in neuronal cell protection by VEGF against glutamate excitotoxicity in primary rat hippocampal neuronal cultures |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | intrinsic characteristics of the neurotoxic initiators (glutamate glutamate vs mutant SOD1 leading to heterogeneities in downstream kinase recruitment and regulation |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | It has become apparent that activation of kinases such as PI3-K or MAPK does not constitute an isolated event but rather |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | become apparent that activation of kinases such as PI3-K or MAPK does not constitute an isolated event but rather represents a |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | Thus it is possible that the PI3-K/Akt PI3-K Akt signaling module recruited by VEGF in our experiments is |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | possible that the PI3-K/Akt PI3-K Akt signaling module recruited by VEGF in our experiments is associated with survival and the activation |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK-related | 2.2 | our experiments is associated with survival and the activation of MAPK-related signaling pathways is primarily related to proliferation in mouse NSC34 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | Thus it is possible that the PI3-K/Akt PI3-K Akt signaling module recruited by VEGF in our experiments is associated |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | activation is essential for implementation of the protective effect by PI3-K on mutant G93A-SOD1-mediated motor neuron-like cell survival |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Our experiments further revealed that Akt activation is essential for implementation of the protective effect by |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | expression of dominant negative Akt blocked the protective function of VEGF while the expression of constitutively active Akt partially prevented mutant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | while the expression of constitutively active Akt partially prevented mutant SOD1-mediated motor neuron-like cell death even in the absence of VEGF |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | SOD1-mediated motor neuron-like cell death even in the absence of VEGF ( Fig 5F |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Indeed expression of dominant negative Akt blocked the protective function of VEGF while the expression of |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | protective function of VEGF while the expression of constitutively active Akt partially prevented mutant SOD1-mediated motor neuron-like cell death even in |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | is now well established as a critical protein activated by PI3-K governing the balance between survival and apoptosis 7 and 13 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | These findings are not surprising since Akt is now well established as a critical protein activated by |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Once phosphorylated Akt has been demonstrated to promote cell survival by inactivation of |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | It is unclear what apoptosis-related targets are specifically repressed by VEGF in the mutant SOD1-infected NSC34 motor neuron-like system |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-infected | 1.7 | apoptosis-related targets are specifically repressed by VEGF in the mutant SOD1-infected NSC34 motor neuron-like system |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | However several lines of evidence suggest that the VEGF/Akt VEGF Akt pathway is particularly important to neuronal survival |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | However several lines of evidence suggest that the VEGF/Akt VEGF Akt pathway is particularly important to neuronal survival |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | exposed to a pre-conditioning hypoxic stimulus up-regulated the expression of VEGF and Akt and the activity of the latter was critical |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.1 | a pre-conditioning hypoxic stimulus up-regulated the expression of VEGF and Akt and the activity of the latter was critical to increased |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | Similarly expression of active Akt suppressed mouse hippocampal neuronal death induced by hypoxia glutamate or |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | In addition activation of Akt was tightly linked to neuronal cell survival after traumatic brain |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Taken together these results suggest that hypoxia modulation of VEGF expression (activity) activity is essential to motor neuron survival |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | We now demonstrate that the activation of PI3-K/Akt PI3-K Akt signaling pathways by VEGF can promote motor neuron-like cell |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | that the activation of PI3-K/Akt PI3-K Akt signaling pathways by VEGF can promote motor neuron-like cell survival in the presence of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | promote motor neuron-like cell survival in the presence of mutant SOD1 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | We now demonstrate that the activation of PI3-K/Akt PI3-K Akt signaling pathways by VEGF can promote motor neuron-like cell survival |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | However since the activation of PI3-K/Akt PI3-K Akt is a transient event ( Fig 4 the long-lasting |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | transient event ( Fig 4 the long-lasting protective function of VEGF on mutant SOD1-mediated motor neuron-like cell death may be due |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | Fig 4 the long-lasting protective function of VEGF on mutant SOD1-mediated motor neuron-like cell death may be due to the modulation |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | However since the activation of PI3-K/Akt PI3-K Akt is a transient event ( Fig 4 the long-lasting protective |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | In summary we have shown that VEGF can protect from mutant SOD1- and oxidative stress-mediated motor neuron-like |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1- | 1.7 | summary we have shown that VEGF can protect from mutant SOD1- and oxidative stress-mediated motor neuron-like cell death in a cell |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | pharmacological and molecular genetic approaches we have demonstrated that PI3-K/Akt PI3-K Akt activation is the primary contributor to the neuroprotective function |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | activation is the primary contributor to the neuroprotective function of VEGF in mouse NSC34 motor neuron-like cells |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | and molecular genetic approaches we have demonstrated that PI3-K/Akt PI3-K Akt activation is the primary contributor to the neuroprotective function of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | Expression of mutant G93A-SOD1 (mSOD1) mSOD1 increased NSC34 motor neuron-like cell death |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 3.7 | (A) A Western analysis of SOD1 expression in NSC34 motor neuron-like cells |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | (B) B Expression of mutant G93A-SOD1 (mSOD1) mSOD1 increased cellular production of reactive oxygen species |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | with WT-SOD1 mutant G93A-SOD1 or treated with hydrogen peroxide or TNF-_amp_#x3b1 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF reduced hydrogen peroxide- TNF-_amp_#x3b1;- and mutant SOD1-mediated NSC34 motor neuron-like |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | VEGF reduced hydrogen peroxide- TNF-_amp_#x3b1;- and mutant SOD1-mediated NSC34 motor neuron-like cell death |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | (A) A VEGF reduced hydrogen peroxide-mediated NSC34 motor neuron-like cell death |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | NSC34 cells were pretreated with 100 ng/ml ng ml of VEGF or vehicle control for 30 min and then exposed to |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-A | 1.2 | A except that cells were treated with different concentrations of TNF-_amp_#x3b1 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF activated MAPK activity in mouse NSC34 motor neuron-like cells |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | VEGF activated MAPK activity in mouse NSC34 motor neuron-like cells |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | with different doses (25_amp_#x2013;200 25_amp_#x2013 200 ng/ml) ng ml of VEGF and then assayed for ERK1/2 ERK1 2 phosphorylation |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 2.7 | ng/ml) ng ml of VEGF and then assayed for ERK1/2 ERK1 2 phosphorylation |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | (B) B The increase of MAPK activity in three independent experiments compared to that of vector |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | Erk1 | 2.7 | independent experiments compared to that of vector control calibrated by Erk1 expression (mean_amp_#xb1;S.E.M.; mean_amp_#xb1 S.E.M. n =3 *statistically significant compared to |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | NSC34 cells were treated with 100 ng/ml ng ml of VEGF for different lengths of time (30_amp_#x2013;180 30_amp_#x2013 180 min and |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | ERK1 | 2.7 | time (30_amp_#x2013;180 30_amp_#x2013 180 min and then assayed for ERK1/2 ERK1 2 phosphorylation |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | (D) D The increase of MAPK activity in three independent experiments compared to that of vector |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | Erk1 | 2.7 | independent experiments compared to that of vector control calibrated by Erk1 expression (mean_amp_#xb1;S.E.M.; mean_amp_#xb1 S.E.M. n =3 *statistically significant compared to |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | VEGF activated PI3-K activity in mouse NSC34 motor neuron-like cells |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | VEGF activated PI3-K activity in mouse NSC34 motor neuron-like cells |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | (A) A NSC34 cells were treated with different doses of VEGF (25_amp_#x2013;200 25_amp_#x2013 200 ng/ml) ng ml and then assayed for |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (25_amp_#x2013;200 25_amp_#x2013 200 ng/ml) ng ml and then assayed for PI3-K activity as described in Materials and methods |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (B) B The increase of PI3-K activity in three independent experiments compared to that of vector |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | NSC34 cells were treated with 100 ng/ml ng ml of VEGF for different lengths of time (30_amp_#x2013;180 30_amp_#x2013 180 min and |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | of time (30_amp_#x2013;180 30_amp_#x2013 180 min and then assayed for PI3-K activity as described in Materials and methods |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (D) D The increase of PI3-K activity in three independent experiments compared to that of vector |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | Activation of PI3-K/Akt PI3-K Akt pathways by VEGF contributed to the protection from mutant |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | Activation of PI3-K/Akt PI3-K Akt pathways by VEGF contributed to the protection from mutant G93A-SOD1-mediated NSC34 motor neuron-like |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.3 | Activation of PI3-K/Akt PI3-K Akt pathways by VEGF contributed to the protection from mutant G93A-SOD1-mediated |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (A) A PI3-K activity inhibitor LY294002 not MAPK activity inhibitor PD98059 contributed to |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 2.2 | (A) A PI3-K activity inhibitor LY294002 not MAPK activity inhibitor PD98059 contributed to the loss of the protection |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (B) B Constitutively active PI3-K catalytic subunit (p110), p110 not constitutively active MEK1 contributed to |
| 16860 | SART3 | squamous cell carcinoma antigen recognized by T cells 3 | p110 | 1.3 | (B) B Constitutively active PI3-K catalytic subunit (p110), p110 not constitutively active MEK1 contributed to the protection from NSC34 |
| 6840 | MAP2K1 | mitogen-activated protein kinase kinase 1 | MEK1 | 2.2 | Constitutively active PI3-K catalytic subunit (p110), p110 not constitutively active MEK1 contributed to the protection from NSC34 cell death from mutant |
| 8979 | PIK3R1 | phosphoinositide-3-kinase, regulatory subunit 1 (alpha) | p85 | 0.6 | (C) C Dominant negative p85 of PI3-K regulatory subunit not dominant negative MEK1 contributed to |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | PI3-K | 2.6 | (C) C Dominant negative p85 of PI3-K regulatory subunit not dominant negative MEK1 contributed to the loss |
| 6840 | MAP2K1 | mitogen-activated protein kinase kinase 1 | MEK1 | 2.2 | Dominant negative p85 of PI3-K regulatory subunit not dominant negative MEK1 contributed to the loss of the protection from NSC34 cell |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | NSC34 cells were treated with 100 ng/ml ng ml of VEGF for different lengths of time (30_amp_#x2013;180 30_amp_#x2013 180 min and |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | of time (30_amp_#x2013;180 30_amp_#x2013 180 min and then assayed for Akt activation as described in Materials and methods |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | (E) E The increase of Akt activation in three independent experiments compared to that of vector |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 4.3 | while dominant negative Akt partially abolished the protective function of VEGF on NSC34 motor neuron survival upon expression of mutant G93A-SOD1 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | (F) F Constitutively active Akt enhanced while dominant negative Akt partially abolished the protective function |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Akt | 0.0 | (F) F Constitutively active Akt enhanced while dominant negative Akt partially abolished the protective function of VEGF on NSC34 motor |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | vascular endothelial growth factor vegf is neurotrophic and also protects from hypoxia induced neuronal injury. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | the landmark discovery that mutations of the copper_amp_#x2013;zinc superoxide dismutase sod1 gene cause a portion of human familial als and that transgenic animal models expressing mutant sod1 mimic human als have contributed significantly to our understanding of human als [ 5 18 37 41 |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | recently vascular endothelial growth factor vegf has been demonstrated to have neurotrophic effects by promoting neuronal cell survival in vitro and in vivo [ 23 26 43 and 45 ]. |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular permeability factor | 1.0 | vegf also known as vascular permeability factor is a dimeric glycoprotein that binds to endothelial cell specific receptors fms like tyrosine kinase flt 1 and fetal liver kinase flk 1 [ 16 and 36 ]. |
| 8975 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | phosphatidylinositol 3 kinase | 1.0 | acting through these receptors vegf is believed to initiate several intracellular signal transduction systems including phosphatidylinositol 3 kinase pi3 k and mitogen activated protein kinase mapk [ 42 ]. |
| 8978 | PIK3CG | phosphoinositide-3-kinase, catalytic, gamma polypeptide | pi3 kinase | 1.0 | pi3 kinase activity assay |
| 1516 | CAT | catalase | catalase | 1.0 | based on our previous study showing that the anti oxidants catalase n acetyl cysteine n ac and the spin trapping molecule 5_amp_#x2032; 5_amp_#x2032; dimethylpryrroline n oxide dmpo were all protective fig 1d and ref [ 32 ] we assume that oxidative stress is at least |
| 727 | ARTN | artemin | neurotrophic factor | 1.0 | several lines of evidence prompted us to examine the effects of vegf on mutant sod1 mediated motor neuron like cell death: i vegf acts as a neurotrophic factor preventing hypoxia ischemia mediated neuronal cell death [ 23 ]; ii increased oxidative stress plays an important role in hypoxia mediated neuronal cell death [ 30 and 33 ]; iii disruption of the hyp |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | horylated akt has been demonstrated to promote cell survival by inactivation of one or more apoptotic factors [ 1 14 15 and 22 ] glycogen synthase kinase 3 forkhead transcription factors [ 8 ] and/or caspase 9 [ 9 ]. |
| 8975 | PIK3CA | phosphoinositide-3-kinase, catalytic, alpha polypeptide | phosphatidylinositol 3 kinase | 1.0 | e proteins|reactive oxygen species|tumor necrosis factor alpha|vascular endothelial growth factor a|vascular endothelial growth factors|hydrogen peroxide|superoxide dismutase 1|superoxide dismutase|1 phosphatidylinositol 3 kinase|protein serine threonine kinases|proto oncogene proteins c akt| |