)| PMID |
18598679 ( ) |
|---|---|
| Title | The NADPH oxidase is involved in lipopolysaccharide-mediated motor neuron injury. |
| Abstract | Recent evidence indicates that neuroinflammation is a key event in amyotrophic lateral sclerosis (ALS). However, the precise impact of inflammation on motor neurons remains elusive. By using organotypic spinal cord slice cultures, we demonstrate that exposure to lipopolysaccharide (LPS) led to the demise of motor neurons in a dose- and time- dependent manner, whereas interneurons were impaired relatively mildly. The ultrastructure of motor neurons showed extensive vacuolation and swollen mitochondria. Motor neurons lacked the expression of calretinin, and BAPTA-AM, an intracellular calcium chelator, ameliorated motor neuron injury, indicating that the low capacity of calcium buffering may partially account for the vulnerability of motor neurons. NADPH oxidase was activated upon LPS challenge, and apocynin, the selective inhibitor of this enzyme, prevented inflammation-mediated toxicity to motor neurons, suggesting that NADPH oxidase may play a critical role in motor neuron death caused by LPS-induced inflammation. Shijiazhuang, Hebei 05000, People's Republic of China. |
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 |
|---|---|---|---|---|
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 24 | nadph oxidase | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 12 | p47 | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 10 | Nox2 | gp91 phox | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 8 | SOD1 | |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | 4 | GAPDH | |
| 1473 | CANX | calnexin | 2 | calnexin | |
| 30306 | PHB2 | prohibitin 2 | 2 | p22 | BAP | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | p67 phox | |
| 15531 | EBNA1BP2 | EBNA1 binding protein 2 | 1 | p40 | |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | 1 | rac1 | |
| 11850 | TLR4 | toll-like receptor 4 | 1 | TLR4 | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | Nox1 | |
| 11848 | TLR2 | toll-like receptor 2 | 1 | TLR2 | |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | 1 | EAAT2 | |
| 7562 | MYD88 | myeloid differentiation primary response gene (88) | 1 | MyD88 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22 phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | Expression of mutant human SOD1 selectively in neurons failed to cause ALS-like disease in mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | Moreover selective reduction of mutant SOD1 levels in microglia extended survival of transgenic SOD1 G37R mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | of mutant SOD1 levels in microglia extended survival of transgenic SOD1 G37R mice ( Boill_amp_#xe9 e et al. 2006 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | In addition in the mutant SOD1 G93A transgenic mice inflammatory responses are present before any evidence |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | Nguyen et al (2004) 2004 triggered the innate immunity of SOD1 G37R transgenic mice with systemic administration of lipopolysaccharide (LPS), LPS |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | NADPH oxidase subunits (gp91 gp91 phox p47 phox and IL-1_amp_#x3b2 mRNA expression were evaluated by semiquantitative RT-PCR |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.5 | and IL-1_amp_#x3b2 mRNA expression were evaluated by semiquantitative RT-PCR using GAPDH gene as internal standard |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | nonfat dry milk before being probed with primary antibodies to p47 phox (1:200, 1 200 Santa Cruz CA |
| 30306 | PHB2 | prohibitin 2 | BAP | 0.5 | 30LPS-treated slices 30LPS 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml LPS 10_amp_#xa0 BAP LPS 10_amp_#xa0 _amp_#x3bc M BAPTA-AM 30_amp_#xa0;_amp_#x3bc;g/ml 30_amp_#xa0 _amp_#x3bc g ml |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Changes in the message level of IL-1_amp_#x3b2 gp91 phox and p47 phox in slice cultures after LPS exposure |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.5 | B Ratio of PCR product from IL-1_amp_#x3b2 to that of GAPDH mRNA |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | C Representative bands of NADPH oxidase subunits gp91 phox and p47 phox mRNA expression in slices treated with medium alone or |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | (D) D Ratio of PCR product from gp91 phox and p47 phox to that of GAPDH mRNA |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.5 | product from gp91 phox and p47 phox to that of GAPDH mRNA |
| 4141 | GAPDH | glyceraldehyde-3-phosphate dehydrogenase | GAPDH | 1.5 | GAPDH was used as an internal control |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Immunoblots (A) A for p47 phox using cytosolic and membranous extracts prepared from the slice |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | the message levels of NADPH oxidase subunits gp91 phox and p47 phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | There was no notable difference in the p47 phox message level between the control and LPS groups ( |
| 30306 | PHB2 | prohibitin 2 | p22 | 0.5 | resting cells composed of two membrane-bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( |
| 15531 | EBNA1BP2 | EBNA1 binding protein 2 | p40 | 0.3 | and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( Babior et |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.0 | components including p47 phox p40 phox p67 phox and rac1/2 rac1 2 ( Babior et al. 2002 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | Two weeks after application of LPS cytosolic subunit p47 phox translocated to the plasma membrane ( Fig 6 A |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | oxidase inhibitor apocynin which significantly reduced LPS-induced PHOX cytosolic subunit p47 phox translocation to the cell membrane ( Fig 6 A |
| 11848 | TLR2 | toll-like receptor 2 | TLR2 | 0.6 | It has been reported that the expression of TLR2 was upregulated in the spinal cord of mutant SOD1 G37R |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | of TLR2 was upregulated in the spinal cord of mutant SOD1 G37R transgenic mice ( Nguyen et al. 2004 and MyD88 |
| 7562 | MYD88 | myeloid differentiation primary response gene (88) | MyD88 | 0.3 | SOD1 G37R transgenic mice ( Nguyen et al. 2004 and MyD88 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 -SOD1 G37R chimeric mice ( Kang and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | ( Nguyen et al. 2004 and MyD88 _amp_#x2212;/_amp_#x2212; _amp_#x2212 _amp_#x2212 -SOD1 G37R chimeric mice ( Kang and Rivest 2007 making it |
| 11850 | TLR4 | toll-like receptor 4 | TLR4 | 1.6 | Lehnardt et al. (2002) 2002 verified that microglia and its TLR4 is necessary for LPS-induced oligodendrocyte injury |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 0.8 | is up-regulated in the spinal cords of ALS patients and SOD1 G93A transgenic mice ( Wu et al. 2006 and deletion |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | mice ( Wu et al. 2006 and deletion of either Nox1 or Nox2 gene significantly slowed disease progression and improved survival |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 2.5 | Wu et al. 2006 and deletion of either Nox1 or Nox2 gene significantly slowed disease progression and improved survival of ALS |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.9 | gp91 phox mRNA expression and the translocation of cytosolic component p47 phox to the membrane following LPS challenge |
| 10940 | SLC1A2 | solute carrier family 1 (glial high affinity glutamate transporter), member 2 | EAAT2 | 1.0 | Corroborating this view are the elevated levels of EAAT2 after exposure to LPS ( Persson et al. 2005 and |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase was activated upon lps challenge and apocynin the selective inhibitor of this enzyme prevented inflammation mediated toxicity to motor neurons suggesting that nadph oxidase may play a critical role in motor neuron death caused by lps induced inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase acting as the functional enzyme in the respiratory burst generates ros not as a byproduct but rather as the primary function of the enzyme system bedard and krause 2007 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | recent studies indicate that ros produced by nadph oxidase could promote neurodegeneration [block and hong 2005] and [li et al. 2005] but the role of nadph oxidase in als remains largely unexplored. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to study the involvement of reactive oxygen species in inflammation induced effects nadph oxidase selective inhibitor apocynin 0.5 and 1_amp_#xa0;mm was coapplied with lps 30_amp_#xa0;_amp_#x3bc;g/ml for 2_amp_#xa0;weeks in the culture medium. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | nadph oxidase subunits gp91 phox p47 phox and il 1_amp_#x3b2; mrna expression were evaluated by semiquantitative rt pcr using gapdh gene as internal standard. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase subunits gp91 phox p47 phox and il 1_amp_#x3b2; mrna expression were evaluated by semiquantitative rt pcr using gapdh gene as internal standard. |
| 1473 | CANX | calnexin | calnexin | 1.0 | bodies were applied and the bands of interest were detected using an odyssey infrared imaging system li cor lincoln nebraska . _amp_#x3b2; actin was used as internal standard of cytosolic protein and calnexin was used as internal standard of membrane protein. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | fig. 5._amp_#xa0;changes in the message level of il 1_amp_#x3b2; gp91 phox and p47 phox in slice cultures after lps exposure. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | c representative bands of nadph oxidase subunits gp91 phox and p47 phox mrna expression in slices treated with medium alone or 30_amp_#xa0;_amp_#x3bc;g/ml lps for 2_amp_#xa0;weeks after 1_amp_#xa0;week in culture. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | c representative bands of nadph oxidase subunits gp91 phox and p47 phox mrna expression in slices treated with medium alone or 30_amp_#xa0;_amp_#x3bc;g/ml lps for 2_amp_#xa0;weeks after 1_amp_#xa0;week in culture. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | d ratio of pcr product from gp91 phox and p47 phox to that of gapdh mrna. |
| 1473 | CANX | calnexin | calnexin | 1.0 | immunoblots a for p47 phox using cytosolic and membranous extracts prepared from the slice cultures. _amp_#x3b2; actin was used as internal standard of cytosolic protein and calnexin was used as internal standard of membrane protein. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase inhibitor apocynin prevented lps induced toxicity to motor neurons. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase and il 1_amp_#x3b2; mrna expression in spinal cord slices treated with lps |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | we also investigated the message levels of nadph oxidase subunits gp91 phox and p47 phox . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we also investigated the message levels of nadph oxidase subunits gp91 phox and p47 phox . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | the mrna expression of gp91 phox in the slices treated with lps significantly increased compared to the controls figs 5 c and d . |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 phox | 1.0 | nadph oxidase also known as phagocytic oxidase phox is a dormant enzyme in resting cells composed of two membrane bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 babior et al. 2002 . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 phox | 1.0 | lso known as phagocytic oxidase phox is a dormant enzyme in resting cells composed of two membrane bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 babior et al. 2002 . |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | nadph oxidase also known as phagocytic oxidase phox is a dormant enzyme in resting cells composed of two membrane bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 babior et al. 2002 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase also known as phagocytic oxidase phox is a dormant enzyme in resting cells composed of two membrane bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 pho |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | gp91 phox is the catalytic core of the enzyme. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | due to its particular construction the functional change of nadph oxidase relies more importantly on subcellular distribution of cytosolic subunits. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | so we next investigated the function of nadph oxidase at protein level and whether it was required for neurotoxicity induced by lps mediated inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we first determined whether nadph oxidase formed an assembled and activated enzyme complex upon lps challenge. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | two weeks after application of lps cytosolic subunit p47 phox translocated to the plasma membrane fig 6 a indicating that nadph oxidase became activated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | next we examined the effect of nadph oxidase inhibitor apocynin which significantly reduced lps induced phox cytosolic subunit p47 phox translocation to the cell membrane fig 6 a . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase is a membrane bound enzyme consisting of multiple subunits. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in addition nadph oxidase derived ros can mediate proinflammatory gene expression and lead to the production of inflammatory cytokines qin et al. 2004 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase is therefore considered a key factor in oxidative stress and inflammatory processes both of which are implicated in the pathogenesis of als. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | we speculated that nadph oxidase might mediate the toxicity to motor neurons. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | this hypothesis is supported by two recent reports that nadph oxidase is up regulated in the spinal cords of als patients and sod1 g93a transgenic mice wu et al. 2006 and deletion of either nox1 or nox2 gene significantly slowed disease progression and improved surviva |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in the present study we found that nadph oxidase was activated as indicated by the up regulation of membranous subunit gp91 phox mrna expression and the translocation of cytosolic component p47 phox to the membrane following lps challenge. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the present study we found that nadph oxidase was activated as indicated by the up regulation of membranous subunit gp91 phox mrna expression and the translocation of cytosolic component p47 phox to the membrane following lps challenge. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | more importantly lps induced inflammation mediated toxicity to motor neurons was markedly ameliorated by the nadph oxidase inhibitor apocynin. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these data provide evidence that nadph oxidase plays an important role in mediating motor neuron injury under inflammatory conditions. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase contributes to the demise of motor neurons caused by lps induced inflammation. |