)| PMID |
16046141 ( ) |
|---|---|
| Title | Apaf1 mediates apoptosis and mitochondrial damage induced by mutant human SOD1s typical of familial amyotrophic lateral sclerosis. |
| Abstract | Several studies have indicated that apoptotic pathways are responsible for the loss of motor neurons that constitute the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we demonstrate that apoptosis induced by the expression of several mutant Cu,Zn superoxide dismutases (SOD1) typical of familial ALS is mediated by Apaf1, a scaffold protein involved in neural development. Using different cell lines of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1, we show that the removal of Apaf1 prevents cells death. Interestingly, intercepting activation of the caspases cascade is also effective in preventing both the mitochondrial damage and the increase in the production of reactive oxygen species induced by fALS-SOD1, even in the presence of cytochrome c release. This death pathway may be crucial also for the pathogenesis of the sporadic form of the disease, where markers of increased oxidative stress and mitochondria damage have been found. Vergata-Santa Lucia, Rome, Italy. |
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 |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 48 | SOD1 | SOD1-mediated | SOD1-induced | SOD1s | superoxide dismutase | |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | 47 | Apaf1 | Apaf1-deficient | |
| 19986 | CYCS | cytochrome c, somatic | 26 | cytochrome c | |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | 15 | caspase 3 | |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | 10 | caspase 9 | |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | 8 | apoptosis inducing factor | AIF | |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | 6 | caspase 1 | |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | 5 | Bcl-2 | bcl2 | bcl 2 | Bcl2 | |
| 2903 | DLG4 | discs, large homolog 4 (Drosophila) | 2 | PSD95 | psd95 | |
| 9717 | PXMP3 | peroxisomal membrane protein 3, 35kDa (Zellweger syndrome) | 1 | paf1 | |
| 7896 | NPAT | nuclear protein, ataxia-telangiectasia locus | 1 | e14 | |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | 1 | p75 | |
| 1912 | CHAT | choline acetyltransferase | 1 | choline acetyltransferase | |
| 1503 | CASP2 | caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2) | 1 | caspase 2 | |
| 7707 | NDUFS1 | NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase) | 1 | NDUFS1 | |
| 6893 | MAPT | microtubule-associated protein tau | 1 | tau | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | the expression of several mutant Cu Zn superoxide dismutases (SOD1) SOD1 typical of familial ALS is mediated by Apaf1 a scaffold |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | dismutases (SOD1) SOD1 typical of familial ALS is mediated by Apaf1 a scaffold protein involved in neural development |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1 we show that the removal of Apaf1 prevents |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | origin and modulating the expression of both mutant SOD1s and Apaf1 we show that the removal of Apaf1 prevents cells death |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | mutant SOD1s and Apaf1 we show that the removal of Apaf1 prevents cells death |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | gene coding for the enzyme Cu Zn superoxide dismutase (SOD1) SOD1 ( Rosen et al. 1993 fALS-SOD1 mutations cause the appearance |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | paradigms (post-mortem post-mortem samples from patients mice transgenic for mutant SOD1 and cell cultures |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 1.7 | often yielded conflicting results converging evidence indicates that the mutant SOD1-mediated cell death observed in ALS is apoptotic in nature (reviewed |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl2 | 1.5 | Mu et al. 1996 and Vukosavic et al. 1999 and Bcl2 prevents death of cells expressing fALS-SOD1 ( Ghadge et al. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | significantly extend the lifespan of transgenic mice overexpressing a fALS-linked SOD1 mutant ( Li et al. 2000 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | role in the initiation of motor neuron death by mutant SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | to be crucial targets of the toxic function of mutant SOD1 ( Mattiazzi et al. 2002 Liu et al. 2004 Pasinelli |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | c becomes part of the apoptosome a complex in which Apaf1 serves as a scaffold protein also for the binding of |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | In this study we have investigated on the role of Apaf1 and the apoptosome in the induction of death in cell |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Our data demonstrate that removal of Apaf1 prevents cell death and mitochondrial damage by intercepting activation of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | coding for wt or G93A G37R G85R and I113T mutant SOD1 were described elsewhere ( Carr_amp_#xec et al. 1997 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Apaf1 expression plasmid was created by cloning of Apaf1 cDNA ( |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Apaf1 expression plasmid was created by cloning of Apaf1 cDNA ( Cecconi et al. 1998 under control of the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | lines transfected for the transient expression of human wild type SOD1 (named named wt or mutant fALS-SOD1 G93A G37R G85R and |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Embryonic Telencefalic Naive Apaf1 (ETNA_amp_#x2212;/_amp_#x2212;) ETNA_amp_#x2212 _amp_#x2212 cell lines were obtained from e14 embryos |
| 7896 | NPAT | nuclear protein, ataxia-telangiectasia locus | e14 | 0.3 | Naive Apaf1 (ETNA_amp_#x2212;/_amp_#x2212;) ETNA_amp_#x2212 _amp_#x2212 cell lines were obtained from e14 embryos of Apaf1 knock-out mice as previously described ( Cozzolino |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | ETNA_amp_#x2212 _amp_#x2212 cell lines were obtained from e14 embryos of Apaf1 knock-out mice as previously described ( Cozzolino et al. 2004 |
| 2903 | DLG4 | discs, large homolog 4 (Drosophila) | PSD95 | 1.3 | neural markers (NeuN, NeuN class III _amp_#x3b2 -tubulin choline acetyltransferase PSD95 and tau Cozzolino et al. 2004 |
| 6893 | MAPT | microtubule-associated protein tau | tau | 0.3 | (NeuN, NeuN class III _amp_#x3b2 -tubulin choline acetyltransferase PSD95 and tau Cozzolino et al. 2004 |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | For cytochrome c and AIF release experiments ETNA cells were harvested in hypotonic buffer (2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Immunoreactive SOD1 was detected with a rabbit polyclonal antibody (Stratagene) Stratagene |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Apaf1 was detected with a rat mAb anti-Apaf1 (clone clone 18H2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Measurement of SOD1 activity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | SOD1 activity was detected as the achromatic band on the violet-colored |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Overexpression of Apaf1 exacerbates apoptotic death induced by fALS-SOD1 in human neuroblastoma |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | 1 A under this condition the total level of immunoreactive SOD1 is highly increased with respect to the parental line and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | line and 1 day after transfection all lines expressing mutant SOD1 show a remarkable decrease in mitochondrial metabolic activity as indicated |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | Materials and methods 48 h after transfection expression of mutant SOD1s induces activation of caspase-3 caspase-9 but not caspase-1 ( Fig |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Cell death induced by mutant SOD1 is prevented by treatment both with pan-caspase inhibitor z-VAD and |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | To analyze whether Apaf1 is involved in mutant SOD1-induced apoptosis we stably transfected SH-SY5Y |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-induced | 1.7 | To analyze whether Apaf1 is involved in mutant SOD1-induced apoptosis we stably transfected SH-SY5Y neuroblastoma cells with a plasmid |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | stably transfected SH-SY5Y neuroblastoma cells with a plasmid coding for Apaf1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | C05 C19 and C20 were chosen for equivalent expression of Apaf1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | results and data from clone C05 (named named SH/Apaf1) SH Apaf1 are shown |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Western blotting with specific anti-Apaf1 antibodies shows that SH/Apaf1 SH Apaf1 neuroblastoma cells express high levels of Apaf1 ( Fig 2 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | that SH/Apaf1 SH Apaf1 neuroblastoma cells express high levels of Apaf1 ( Fig 2 A |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | In this conditions no Apaf1 expression is detectable in total cell lysates from control cells |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | total cell lysates from control cells although SH-SY5Y do express Apaf1 as assessed by us in immunoprecipitation experiments (not not shown |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Transient transfection of control SH cells or SH/Apaf1 SH Apaf1 cells with wtSOD1 or G93A-SOD1 mutant elicits high level comparable |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | of caspase-3 is dramatically increased only in G93A-expressing SH/Apaf1 SH Apaf1 cells as compared to G93A-transfected SH cells ( Fig 2 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | 20-fold increase of apoptotic nuclei is observed in SH/Apaf1 SH Apaf1 cells expressing the mutant SOD1 with respect to untransfected control |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | is observed in SH/Apaf1 SH Apaf1 cells expressing the mutant SOD1 with respect to untransfected control SH cells |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Deletion of Apaf1 prevents apoptotic death induced by fALS-SOD1 in mouse neuronal cells |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | order to establish an experimental system where the role of Apaf1 in fALS-SOD1-induced cell death could be thoroughly studied embryonal cortical |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | thoroughly studied embryonal cortical cells from a control mouse (Apaf1+/+) Apaf1 or a mouse knocked-out for Apaf1 (Apaf1_amp_#x2212;/_amp_#x2212;) Apaf1_amp_#x2212 _amp_#x2212 have |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | a control mouse (Apaf1+/+) Apaf1 or a mouse knocked-out for Apaf1 (Apaf1_amp_#x2212;/_amp_#x2212;) Apaf1_amp_#x2212 _amp_#x2212 have been isolated and immortalized by the |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | ETNA_amp_#x2212;/_amp_#x2212; ETNA_amp_#x2212 _amp_#x2212 cells do not express Apaf1 and the absence of this adapter provides them with a |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | We have observed that Apaf1 deletion also provides these cells with a complete resistance to |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Cytochrome c release induced by fALS-SOD1 is independent of Apaf1 expression |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | cytochrome c release in cells expressing either fALS-SOD1s or wild-type SOD1 ETNA cells were transfected with cDNA coding for GFP-SOD1s fusion |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | tag does not affect the dismutase activity of the various SOD1s ( Fig 4 A GFP-G93A and GFP-A4V mutants are similar |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | As shown in Fig 4 C overexpression of mutant SOD1s causes the appearance of large intracellular aggregates (not not visible |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | large intracellular aggregates (not not visible in cells overexpressing wild-type SOD1 in ETNA cells as in various other experimental paradigms ( |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | expressing different fALS-SOD1s display cytochrome c release independently from the Apaf1 genotype ( Figs 4 B_amp_#x2013 D |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | that other mitochondrial factors involved in apoptotic pathways such as AIF ( Fig 4 and Fig 5 and EndoG (not not |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | not shown are not affected by the expression of mutant SOD1s in this system |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1-deficient | 1.1 | As shown in Fig 6 A Apaf1-deficient ETNA cells are completely resistant to fALS-SOD1-induced mitochondrial impairment as |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | On the opposite cotransfection of mutant SOD1s with Apaf1 in ETNA_amp_#x2212;/_amp_#x2212; ETNA_amp_#x2212 _amp_#x2212 cells significantly restores the |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | On the opposite cotransfection of mutant SOD1s with Apaf1 in ETNA_amp_#x2212;/_amp_#x2212; ETNA_amp_#x2212 _amp_#x2212 cells significantly restores the toxic effect |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | in these cells is exclusively due to the lack of Apaf1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Again protein oxidation induced by mutant SOD1 in ETNA+/+ ETNA cells is significantly reduced in cells lacking |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | in ETNA+/+ ETNA cells is significantly reduced in cells lacking Apaf1 ( Fig 6 C |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | has been suggested also by studies where targeting of mutant SOD1 specifically to the nucleus cytosol and in the mitochondrion matrix |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | pore causing leakage of cytochrome c and apoptosis-inducing factor (AIF) AIF ( Friedlander 2003 were suggested to play a role in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | classic_amp_#x201d apoptosis is involved in the motor neuron death in SOD1 mutant mice and perhaps also in ALS patients |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | further insight in this process by studying the contribution of Apaf1 to cell death induced by different mutants SOD1s |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | contribution of Apaf1 to cell death induced by different mutants SOD1s |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | loops (G37R, G37R I113T thus representing every class of mutant SOD1 found in patients except those truncated at the C-term end |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1 we have observed that indeed Apaf1 is a |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | origin and modulating the expression of both mutant SOD1s and Apaf1 we have observed that indeed Apaf1 is a key factor |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | both mutant SOD1s and Apaf1 we have observed that indeed Apaf1 is a key factor in the noxious function of fALS-SOD1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | factor in the noxious function of fALS-SOD1 while overexpression of Apaf1 exacerbates the induction of apoptosis ( Fig 2 its removal |
| 10876 | SIGLEC7 | sialic acid binding Ig-like lectin 7 | p75 | 0.3 | critical caspase substrate in the mitochondria and that cleavage of p75 by caspases is responsible for disruption of electron transport leading |
| 7707 | NDUFS1 | NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase) | NDUFS1 | 0.0 | Interestingly Ricci et al have recently shown that NDUFS1 the 75 kDa subunit of respiratory complex I is a |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | direct consequence of the postulated pro-oxidant toxic function of mutant SOD1 ( Valentine 2002 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Mutant SOD1 may either exert some aberrant chemistry specifically inside (or or |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Indeed the intracellular localization of wild-type and mutant SOD1 has recently been questioned |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | previous studies reporting that a fraction of the normally cytosolic SOD1 protein is detected within the mitochondrion probably either at the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | al have reported that multiple disease-causing mutants but not wild-type SOD1 are recruited to mitochondria but only in affected tissues ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | of protein are successfully imported but nearly constant amounts of SOD1 mutants and covalently damaged adducts of them accumulate |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | damage from action of spinal cord-specific factors that recruit mutant SOD1 to spinal mitochondria as the basis for their selective toxicity |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | to being in the mitochondrial outer membrane and intermembrane space SOD1 is also localized in the mitochondrial matrix |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | Furthermore aberrant SOD1 macromolecular aggregates are formed in the matrix of brain mitochondria |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1s | 1.7 | Aggregation of mitochondrial mutant SOD1s may also have a role in altering the functionality of |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.5 | al have reported that both wt- and mutSOD1 bind to Bcl-2 an anti-apoptotic protein located on the cytoplasmic face of outer |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | Bcl-2 | 1.5 | of outer mitochondria membranes and have suggested that entrapment of Bcl-2 by large mutSOD1 aggregates may deplete motor neurons of this |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | These results suggest a mechanism by which mutant SOD1 can disrupt the association of proteins involved in cell survival |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | causes altering mitochondria functionality or from abnormal aggregation of wild-type SOD1 together with mitochondria proteins |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | (A) A Western blot analysis of SOD1 expression in SH-SY5Y cells untransfected or transiently transfected for 48 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | h with wtSOD1 and G93A G37R G85R and I113T mutant SOD1 20 _amp_#x3bc g of total cell lysates was loaded |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Fig 2._amp_#xa0 Overexpression of Apaf1 exacerbates apoptotic death induced by fALS-SOD1 in human neuroblastoma |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | A Na_amp_#xef ve SH-SY5Y cells or SH-SY5Y cells stably overexpressing Apaf1 (SH/Apaf1) SH Apaf1 were transiently transfected with wtSOD1 or with |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | SH-SY5Y cells or SH-SY5Y cells stably overexpressing Apaf1 (SH/Apaf1) SH Apaf1 were transiently transfected with wtSOD1 or with the G93A-SOD1 mutant |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | of total cell lysates was analyzed for the expression of SOD1 and Apaf1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | cell lysates was analyzed for the expression of SOD1 and Apaf1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | Fig 3._amp_#xa0 Deletion of Apaf1 prevents apoptotic death induced by fALS-SOD1 in mouse neuronal cells |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | 4._amp_#xa0 Cytochrome c release induced by fALS-SOD1 is independent of Apaf1 expression |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.2 | After 24 h SOD1 activity was detected on 10% polyacrylamide gel by the NBT/riboflavin |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | mutants were assessed for the presence of cytochrome c and AIF by Western blot |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | untransfected ETNA cells were used as a positive control for AIF and cytochrome c expression |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | Fig 5._amp_#xa0 ETNA cells retain mitochondrial AIF upon fALS-SOD1 expression |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | AIF | 0.6 | confocal immunofluorescence microscopy staining of cytochrome c (green) green and AIF (red) red in ETNA cells 48 h after transfection with |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | wtSOD1 or G93A G37R G85R and I113T-SOD1 mutants with (Apaf1) Apaf1 or without a plasmid coding for Apaf1 |
| 576 | APAF1 | apoptotic peptidase activating factor 1 | Apaf1 | 2.1 | mutants with (Apaf1) Apaf1 or without a plasmid coding for Apaf1 |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | vation of the caspases cascade is also effective in preventing both the mitochondrial damage and the increase in the production of reactive oxygen species induced by fals sod1 even in the presence of cytochrome c release. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mitochondria alterations membrane depolarization decreased activity of respiratory complexes cytochrome c release and oxidative stress increased ros flux oxidatively modified proteins seem likely candidates to explain many facets of als because of their early occurrence in experimental models and in pati |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | als occurs both as a sporadic and as a familial dominantly inherited disease fals and about one fifth of fals patients have mutations in the gene coding for the enzyme cu zn superoxide dismutase sod1 rosen et al. 1993 . fals sod1 mutations cause the appearance of a pro oxidant pro apoptotic function in a typically anti oxidant anti apoptotic enzyme rabizadeh et al. 1995 wiedau pazos et al. 1 |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | t al. 1997 and prolongs life in a transgenic mouse model kostic et al. 1997 ; caspases 1 and 3 have consistently been shown to play an important role in the death of motor neurons in this disease and caspase 9 is activated in spinal motor neurons of human als subjects inoue et al. 2003 . |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl2 | 1.0 | members of the bcl gene family show altered expression in post mortem samples from sporadic and familial als patients and in experimental models as well mu et al. 1996 and vukosavic et al. 1999 and bcl2 prevents death of cells expressing fals sod1 ghadge et al. 1997 and prolongs life in a transgenic mouse model kostic et al. 1997 ; caspases 1 and 3 have consistently been shown to play an important r |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | of apoptosis by oxidative stress is a feature observed in several experimental paradigms cai and jones 1998 and luetjens et al. 2000 and oxidative stress mediated mitochondrial dysfunction leading to cytochrome c release plays an important role in the initiation of motor neuron death by mutant sod1. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | in spinal cord specimens of both als patients and in the mice model for fals evidence of prominent recruitment of the mitochondrial apoptotic pathway has been documented by the observation of cytochrome c release and by the observation that prevention of cytochrome c release prolongs the lifespan of transgenic sod1 g93a mice zhu et al. 2002 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | release and by the observation that prevention of cytochrome c release prolongs the lifespan of transgenic sod1 g93a mice zhu et al. 2002 . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | upon release from mitochondria cytochrome c becomes part of the apoptosome a complex in which apaf1 serves as a scaffold protein also for the binding of pro caspase 9 the apoptosome recruits and processes caspase 9 to form a holoenzyme complex which in turn recruits and activates the effector caspases cecconi 1999 . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | the apoptosome recruits and processes caspase 9 to form a holoenzyme complex which in turn recruits and activates the effector caspases cecconi 1999 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | upon release from mitochondria cytochrome c becomes part of the apoptosome a complex in which apaf1 serves as a scaffold protein also for the binding of pro caspase 9 the apoptosome recruits and processes caspase 9 to form a holoenzyme complex |
| 1503 | CASP2 | caspase 2, apoptosis-related cysteine peptidase (neural precursor cell expressed, developmentally down-regulated 2) | caspase 2 | 1.0 | therefore the apoptosome has a crucial role in the activation of several caspases such as caspase 2 3 6 7 8 and 10 adams and cory 2002 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | our data demonstrate that removal of apaf1 prevents cell death and mitochondrial damage by intercepting activation of the caspases cascade even in the presence of cytochrome c release. |
| 2903 | DLG4 | discs, large homolog 4 (Drosophila) | psd95 | 1.0 | ed to differentiate both etna+/+ and _amp_#x2212;/_amp_#x2212; cells display neurite outgrowth and the upregulation of some neural markers neun class iii _amp_#x3b2; tubulin choline acetyltransferase psd95 and tau; cozzolino et al. 2004 . |
| 1912 | CHAT | choline acetyltransferase | choline acetyltransferase | 1.0 | nal precursors; when induced to differentiate both etna+/+ and _amp_#x2212;/_amp_#x2212; cells display neurite outgrowth and the upregulation of some neural markers neun class iii _amp_#x3b2; tubulin choline acetyltransferase psd95 and tau; cozzolino et al. 2004 . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | the broad caspase inhibitor zvad fmk 100 _amp_#x3bc;m; calbiochem and the caspase 9 specific inhibitor zlehd fmk 100 _amp_#x3bc;m; calbiochem were added at this time. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | caspase 1 and caspase 3 activities were determined by measuring the rates of 7 amido 4 methylcoumarin amc release from synthetic caspase substrates: ac yvad amc for caspase 1 and ac devd amc for caspase 3 calbiochem . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | caspase 1 and caspase 3 activities were determined by measuring the rates of 7 amido 4 methylcoumarin amc release from synthetic caspase substrates: ac yvad amc for caspase 1 and ac devd amc for caspase 3 calbiochem . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | specific activity was demonstrated by the use of the caspase 1 and caspase 3 inhibitors ac yvad cho and ac devd cho respectively that completely block the development of fluorescence due to the cleaved product. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | specific activity was demonstrated by the use of the caspase 1 and caspase 3 inhibitors ac yvad cho and ac devd cho respectively that completely block the development of fluorescence due to the cleaved product. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | for cytochrome c and aif release experiments etna cells were harvested in hypotonic buffer 2 mm mgcl 2 10 mm kcl 10 mm tris_amp_#x2013;hcl ph 7.6 supplemented with protease inhibitor cocktail sigma and incubated for |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | caspase 1 was detected with a rabbit polyclonal antibody sigma aldrich recognizing the 45 kda pro enzyme and the 20 kda active subunit. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | caspase 3 activity was detected using a rabbit polyclonal antibody cell signaling specifically reacting with the cleaved 17/19 kda fragments of active caspase 3. |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | caspase 9 activity was detected using a rabbit polyclonal antibody cell signaling specifically reacting with the cleaved fragments of active caspase 9. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mouse monoclonal anti cytochrome c antibody was purchased from bd bioscience. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | an anti cytochrome c monoclonal antibody clone 6h2.b4 pharmingen an anti cytochrome c polyclonal antibody santa cruz an anti aif monoclonal antibody clone e1 santa cruz and an anti endog polyclonal antibody prosci incorporated were used. |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | ring that the percentage of transfected cells was estimated around 30% see materials and methods . 48 h after transfection expression of mutant sod1s induces activation of caspase 3 caspase 9 but not caspase 1 fig 1 c . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | icularly conspicuous considering that the percentage of transfected cells was estimated around 30% see materials and methods . 48 h after transfection expression of mutant sod1s induces activation of caspase 3 caspase 9 but not caspase 1 fig 1 c . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | onspicuous considering that the percentage of transfected cells was estimated around 30% see materials and methods . 48 h after transfection expression of mutant sod1s induces activation of caspase 3 caspase 9 but not caspase 1 fig 1 c . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | cell death induced by mutant sod1 is prevented by treatment both with pan caspase inhibitor z vad and by caspase 9 inhibitor lehd fig 1 d . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | transient transfection of control sh cells or sh/apaf1 cells with wtsod1 or g93a sod1 mutant elicits high level comparable expression of the two proteins in both cell lines fig 2 a but activation of caspase 3 is dramatically increased only in g93a expressing sh/apaf1 cells as compared to g93a transfected sh cells fig 2 b . |
| 9717 | PXMP3 | peroxisomal membrane protein 3, 35kDa (Zellweger syndrome) | paf1 | 1.0 | stable cell lines have been named etna e mbryonic t elencephalic n aive a paf1 ; etna+/+ and etna_amp_#x2212;/_amp_#x2212; cell lines have been preliminary characterized both in basal growth conditions and after further differentiation cozzolino et al. 2004 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | etna_amp_#x2212;/_amp_#x2212; cells do not express apaf1 and the absence of this adapter provides them with a complete resistance to caspase 3 activation elicited by a classic pro apoptotic agent such as staurosporine cozzolino et al. 2004 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | we have observed that apaf1 deletion also provides these cells with a complete resistance to activation of caspase 3 induced by several fals sod1s and observed in control etna+/+ cells 24 h after transfection with the cdna coding for the mutant protein fig 3 a . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | cytochrome c release induced by fals sod1 is independent of apaf1 expression |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mitochondrial damage and cytochrome c release are pro apoptotic features observed in several experimental paradigms for fals see introduction . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | to compare cytochrome c release in cells expressing either fals sod1s or wild type sod1 etna cells were transfected with cdna coding for gfp sod1s fusion proteins. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | furthermore while no cytochrome c release is observed in cells expressing gfp or the wild type enzyme both etna_amp_#x2212;/_amp_#x2212; and etna+/+ cells expressing different fals sod1s display cytochrome c release independently from the apaf1 genotype figs 4 b_amp_#x2013;d . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mitochondrial release of pro apoptotic factors induced by fals sod1 is specific for cytochrome c ; indeed we have observed that other mitochondrial factors involved in apoptotic pathways such as aif fig 4 and fig 5 and endog not shown are not affected by the expression of mutant sod1s in this sy |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | it is widely believed that activation of the apoptosome followed by caspase 9 and caspase 3 activation plays a central role in cell death in the nervous system yuan and yankner 2000 . |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | it is widely believed that activation of the apoptosome followed by caspase 9 and caspase 3 activation plays a central role in cell death in the nervous system yuan and yankner 2000 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | mitochondrial membrane depolarization decreased activity of respiratory complexes and cytochrome c release occur at the asymptomatic stage in fals sod1 transgenic mice bendotti et al. 2001 and jung et al. 2002 and in cultured cells expressing the mutant protein carr_amp_#xec; et al. 1997 beal 2000 |
| 8768 | AIFM1 | apoptosis-inducing factor, mitochondrion-associated, 1 | apoptosis inducing factor | 1.0 | leading to bioenergetic failure in the motor neurons bendotti et al. 2001 and jung et al. 2002 and to alteration in the mitochondrial permeability transition pore causing leakage of cytochrome c and apoptosis inducing factor aif friedlander 2003 were suggested to play a role in the mitochondrial dependent motor neuron death through the activation of a caspase mediated cascade leading to programmed cell death. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | respiratory chain leading to bioenergetic failure in the motor neurons bendotti et al. 2001 and jung et al. 2002 and to alteration in the mitochondrial permeability transition pore causing leakage of cytochrome c and apoptosis inducing factor aif friedlander 2003 were suggested to play a role in the mitochondrial dependent motor neuron death through the activation of a caspase mediated cascade leading to prog |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | we have observed that indeed apaf1 is a key factor in the noxious function of fals sod1: while overexpression of apaf1 exacerbates the induction of apoptosis fig 2 its removal prevents activation of caspase 3 even in the presence of cytochrome c release fig 3 and fig 4 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | 1 is a key factor in the noxious function of fals sod1: while overexpression of apaf1 exacerbates the induction of apoptosis fig 2 its removal prevents activation of caspase 3 even in the presence of cytochrome c release fig 3 and fig 4 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | either exert some aberrant chemistry specifically inside or on the surface of mitochondria or interfere with cytoplasmic functions modulating mitochondria functionality: both could lead to release of cytochrome c activation of the caspase cascade and impairment in the respiratory chain atp depletion and changes in the membrane permeability. |
| 990 | BCL2 | B-cell CLL/lymphoma 2 | bcl 2 | 1.0 | pasinelli et al. have reported that both wt and mutsod1 bind to bcl 2 an anti apoptotic protein located on the cytoplasmic face of outer mitochondria membranes and have suggested that entrapment of bcl 2 by large mutsod1 aggregates may deplete motor neurons of this anti apoptotic protein pasinelli et al. 2004 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | in a recent paper kirkinezos et al. have reported that cytochrome c association with the inner mitochondrial membrane is impaired in the cns of g93a sod1 mice kirkinezos et al. 2005 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | c left panel: sh sy5y cells were transfected as in panel a. after 48 h equal amounts 30 _amp_#x3bc;g of clear cell lysates were incubated with 20 _amp_#x3bc;m ac yvad amc for caspase 1 and ac devd amc for caspase 3 . |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | t panel: sh sy5y cells were transfected as in panel a. after 48 h equal amounts 30 _amp_#x3bc;g of clear cell lysates were incubated with 20 _amp_#x3bc;m ac yvad amc for caspase 1 and ac devd amc for caspase 3 . |
| 1499 | CASP1 | caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta, convertase) | caspase 1 | 1.0 | right panel: caspase 1 caspase 3 and caspase 9 activity were also assessed by western blot. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | right panel: caspase 1 caspase 3 and caspase 9 activity were also assessed by western blot. |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | right panel: caspase 1 caspase 3 and caspase 9 activity were also assessed by western blot. |
| 1511 | CASP9 | caspase 9, apoptosis-related cysteine peptidase | caspase 9 | 1.0 | ication of apoptotic nuclei of sh sy5y transfected with wtsod1 or g37r g85r and i113t sod1 for the indicated periods of time in the absence or in the presence of 100 _amp_#x3bc;m zlehd fmk a specific caspase 9 inhibitor or zvad fmk a pan caspase inhibitor. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | b cells were treated as in panel a and analyzed for caspase 3 activation 24 h after transfection. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | a left panel: caspase 3 activity was assayed in cells 24 h after transient transfection with either wtsod1 or g93a g37r g85r and i113t sod1 mutants. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | caspase 3 activity is expressed as arbitrary fluorescence units afu n _amp_#xa0;=_amp_#xa0;3 . 100 _amp_#x3bc;m zvad fmk a pan caspase inhibitor was used. |
| 1504 | CASP3 | caspase 3, apoptosis-related cysteine peptidase | caspase 3 | 1.0 | right panel: caspase 3 activity was also assessed by western blot. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | gfp green cytochrome c red and merged patterns of the same representative fields are shown. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | c the proportion of gfp positive cells releasing cytochrome c was scored n _amp_#xa0;=_amp_#xa0;3 . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | d cytosolic fractions of etna cells transfected for 24 h with wtsod1 or g93a g37r g85r and i113t sod1 mutants were assessed for the presence of cytochrome c and aif by western blot. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | extracts from the mitochondrial fraction of untransfected etna cells were used as a positive control for aif and cytochrome c expression. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | double labeling confocal immunofluorescence microscopy staining of cytochrome c green and aif red in etna cells 48 h after transfection with wtsod1 gfp g93a sod1 gfp g85r sod1 gfp and a4v sod1 gfp. |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | white arrowheads point to cells with released cytochrome c . |