HUGO ID Detailed Result 990

HUGO ID 990
Symbol BCL2
Name B-cell CLL/lymphoma 2
#Occurrence 139
#Paper 16

 

PMID Match String Actual String Score Flanking text Edited by Edit
10671549Bcl-2Bcl-24.3susceptibility of the WT cells to higher and more stable Bcl-2 and decreased reactive oxygen species 
10671549Bcl-2Bcl-24.3Furthermore G93A cells showed a significant decrease of Bcl-2 expression and as target of NO-derived radicals showed lower cytochrome 
10671549Bcl-2Bcl-24.3Constitutive expression of high Bcl-2 protein levels by transfection experiments has proven that Bcl-2 or 
10671549Bcl-2Bcl-24.3high Bcl-2 protein levels by transfection experiments has proven that Bcl-2 or related family members can protect from NO-mediated apoptosis ( 
10671549Bcl-2Bcl-24.3cells is associated with a canonical sequence of events including Bcl-2 p53 and p21 modulation cytochrome c release in the cytosol 
10671549Bcl-2Bcl-24.3p53 p21 and Bcl-2 Proteins Detection--Cell pellet was resuspended in lysis buffer containing 10 
10671549Bcl-2Bcl-24.310 (for for p53 or 12% (for for p21 and Bcl-2 polyacrylamide gel 
10671549Bcl-2Bcl-24.3on Bax and/or and or Bid two members of the Bcl-2 protein family ( 57 
10671549Bcl-2Bcl-24.3In our experiments Bcl-2 was down-regulated by the GSNO treatment in SH-SY5Y cells whereas 
10671549Bcl-2Bcl-24.3prone to NO-induced apoptosis we propose a causative role for Bcl-2 in the increased susceptibility of G93A cells to apoptosis 
10671549Bcl-2Bcl-24.3It has been suggested that the antiapoptotic effects of Bcl-2 be at least in part due to its antioxidant activity 
10671549Bcl-2Bcl-24.3modulators of physiological signal transduction ( 60 is increased when Bcl-2 is down-regulated 
10671549Bcl-2Bcl-24.3A vicious circle including down-regulation of Bcl-2 and deviating redox activity of copper in the G93A mutant 
10671549Bcl-2Bcl-24.3Bcl-2 content of SH-SY5Y cells and effects on it by Cu 
10671549Bcl-2Bcl-24.3Bcl-2 immunoreactive protein was detected by Western blotting using a monoclonal 
10671549Bcl2Bcl21.0Cytochrome c Release Caspase Activation p53 Accumulation p21 Increase and Bcl2 Down-regulation-- To examine the sequence of events occurring upon GSNO 
10671549Bcl-2Bcl-24.3Bcl-2 protein modulation is responsible for cell survival or suicide constitutive 
10671549Bcl-2Bcl-24.3responsible for cell survival or suicide constitutive expression of high Bcl-2 protein levels by transfection experiments has proven that Bcl-2 or 
10671549Bcl-2Bcl-24.3high Bcl-2 protein levels by transfection experiments has proven that Bcl-2 or related family members can protect cells from NO-mediated apoptosis 
10671549Bcl-2Bcl-24.3analysis untreated SH-SY5Y and WT cells express high levels of Bcl-2 protein whereas G93A cells show a much lower content (Fig 
10671549Bcl-2Bcl-24.3content (Fig Fig 4 48 h of GSNO treatment decreased Bcl-2 expression although to a different extent in particular Bcl-2 content 
10671549Bcl-2Bcl-24.3decreased Bcl-2 expression although to a different extent in particular Bcl-2 content of G93A cells was at the limit of detection 
11679167Bcl-2Bcl-22.6been identified as being major regulators of apoptosis including the Bcl-2 family and caspases 
11679167Bcl-2Bcl-22.6The Bcl-2 family of proteins consist of anti-apoptotic proteins such as Bcl-2 
11679167Bcl-2Bcl-22.6Bcl-2 family of proteins consist of anti-apoptotic proteins such as Bcl-2 and Bcl-x(L), Bcl-x L and pro-apoptotic proteins such as Bax 
11679167Bcl-2Bcl-22.6lacking superoxide dismutase is extended by overexpressing the anti-apoptotic protein Bcl-2 ( Longo et al. 1999 
11679167Bcl-2Bcl-22.6The regulatory role of the Bcl-2 members e.g. depends on their ability to regulate the mitochondrial 
11679167Bcl-2Bcl-22.6In yeast Bcl-2 proteins interact with the voltage-dependent anion channel (VDAC) VDAC and 
12392777Bcl-2Bcl-21.3the expression of the so-called inhibitor-of apoptosis proteins (IAPs), IAPs Bcl-2 and calbindins 179 and 270 
14739060Bcl2Bcl20.0the release of apoptogenic mitochondrial mediators _amp_#x2022 Pro-apoptotic members of Bcl2 family _amp_#x2022 elevated levels of intra-cellular calcium such as that 
15850589BCL2bcl20.0Treatment with inhibitors of MPTP opening and overexpression of bcl2 which inhibits the opening of MPTP under stressful conditions delayed 
15896810Bcl-2Bcl-21.0as increased expression of heat shock proteins antioxidant enzymes and Bcl-2 may be triggered to withstand all the above mentioned pathogenic 
16046141Bcl2Bcl21.5Mu et al. 1996 and Vukosavic et al. 1999 and Bcl2 prevents death of cells expressing fALS-SOD1 ( Ghadge et al. 
16046141Bcl-2Bcl-21.5al have reported that both wt- and mutSOD1 bind to Bcl-2 an anti-apoptotic protein located on the cytoplasmic face of outer 
16046141Bcl-2Bcl-21.5of outer mitochondria membranes and have suggested that entrapment of Bcl-2 by large mutSOD1 aggregates may deplete motor neurons of this 
16050975Bcl-2Bcl-21.8al. 2000 and the overexpression of the mitochondrial anti-apoptotic protein Bcl-2 ( Kostic et al. 1997 slow motor neuron degeneration and 
16050975Bcl-2Bcl-21.8harmful protein-protein interactions is the binding of mutant SOD1 with Bcl-2 ( Pasinelli et al. 2004 
16050975Bcl-2Bcl-21.8mitochondria mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2 ( Pasinelli et al. 2004 affect mitochondrial import by interfering 
16242643Bcl-2Bcl-26.2In addition malonate-induced down-regulation of the antiapoptotic gene Bcl-2 was not prevented by minocycline controversially the mechanism previously proposed 
16242643Bcl-2Bcl-26.2the down-regulation of caspases and iNOS and the up-regulation of Bcl-2 have been documented recently ( Wang et al. 2004 
16242643Bcl-2Bcl-26.2of iNOS caspase-3 -8 and -9 and the antiapoptotic gene Bcl-2 in malonate-treated cells 
16242643Bcl-2Bcl-26.2mM malonate caused a significant down-regulation of the antiapoptotic gene Bcl-2 ( Fig 6 B 
16242643Bcl-2Bcl-26.2Therefore we studied whether minocycline would prevent the down-regulation of Bcl-2 gene expression induced by malonate 
16242643Bcl-2Bcl-26.2lack of protective effect failed to block the down-regulation of Bcl-2 caused by malonate 
16242643Bcl-2Bcl-26.2as iNOS it decreases the mRNA of the antiapoptotic protein Bcl-2 an effect that was not abrogated by minocycline 
16242643Bcl-2Bcl-26.2Conversely we did find a significant down-regulation of Bcl-2 expression after a 24-h malonate exposure 
16242643Bcl-2Bcl-26.2It should be noted that the up-regulation of Bcl-2 gene expression has been recently proposed as a mechanism mediating 
16242643Bcl-2Bcl-26.2present work this drug failed to reverse the down-regulation of Bcl-2 induced by malonate treatment nor induced Bcl-2 expression by itself 
16242643Bcl-2Bcl-26.2the down-regulation of Bcl-2 induced by malonate treatment nor induced Bcl-2 expression by itself 
16242643Bcl-2Bcl-26.2not affect iNOS caspase-3 -8 and -9 but significantly reduces Bcl-2 mRNA expression levels mRNA expression in malonate-treated cerebellar granular cells 
16242643Bcl-2Bcl-26.2(B) B Effect of malonate on Bcl-2 mRNA expression levels 
16242643Bcl-2Bcl-26.2Minocycline pre-treatment fails to avoid the Bcl-2 down-regulation induced by malonate 
16624679Bcl-2Bcl-21.3Interestingly Bcl-2 which has protective activity against oxidative stress 24 and prevents 
16624679Bcl-2Bcl-2-like1.5II (HK), HK cyclophilin D (Cyp-D) Cyp-D and Bax/Bcl-2-like Bax Bcl-2-like proteins (Bax, Bax Bak Bcl-2 
16624679Bcl-2Bcl-21.3(Cyp-D) Cyp-D and Bax/Bcl-2-like Bax Bcl-2-like proteins (Bax, Bax Bak Bcl-2 
17105868Bcl-2Bcl-21.3The ratio of apoptotic cell death genes Bax to Bcl-2 is increased at both the mRNA and protein level in 
17105868Bcl-2Bcl-21.3spinal cord mitochondria but not liver mitochondria and binds to Bcl-2 (Pasinelli Pasinelli et al. 2004 
17105868Bcl-2Bcl-21.3Altered expression and dysfunction of Bcl-2 may contribute to the activation of mitochondrial apoptosis machinery such 
17105868Bcl-2Bcl-21.3In support of this idea overexpression of Bcl-2 or the caspase inhibitory protein XIAP prolongs survival and improves 
17105868Bcl-2Bcl-21.3effect may be attributable to interaction of mutant SOD1 and Bcl-2 causing mitochondrial dysfunction and subsequently increased sensitivity to oxidative stress 
17496232Bcl-2Bcl-21.3ONOO result in DNA damage p53 accumulation increased Bax/Bcl-2, Bax Bcl-2 cytochrome c (cyt cyt c release and caspase activation 
17496232Bcl-2Bcl-21.3S -nitrosylation and inhibition of caspases increase of HSPs and Bcl-2 and activation of Akt/PKB, Akt PKB which induces cytoprotective gene 
17496232Bcl-2Bcl-21.3hand proapoptotic effects of NO include inhibition of NF-kappaB decreased Bcl-2 expression ( 87 -89 118 and increased p53 expression both 
17496232Bcl-2Bcl-21.3that cleave specific aspartate residues in other regulatory proteins like Bcl-2 Bax and MEKK (for for review see Ref 83 
17496232Bcl-2Bcl-21.3gene is associated with embryo lethality many antiapoptotic pathways like Bcl-2 are induced by NF-kappaB. 
7764323bcl 2bcl 21.0free radical scavengers|free radicals|proteins|proto oncogene proteins|proto oncogene proteins c bcl 2|reactive oxygen species|superoxide dismutase|  
7841373bcl 2bcl 21.0bcl 2 protein expression in aged brain and neurodegenerative diseases.  
7841373bcl 2bcl 21.0the proto oncogene bcl 2 is involved in the regulation of cell death and is able to block apoptosis in neurones through reduced generation of reactive oxygen species ros .  
7841373bcl 2bcl 21.0we have studied the immunohistochemical expression of bcl 2 protein in the aged brain and in various human neurodegenerative diseases.  
7841373bcl 2bcl 21.0in all cases bcl 2 was strongly enriched within lipofuscin and autophagic vacuoles of neurones glial and vascular cells.  
7841373bcl 2bcl 21.0our data show that accumulation of bcl 2 is not disease specific and represents a general cellular response which accompanies the increased formation of lipofuscin.  
7841373bcl 2bcl 21.0since oxidative stress is directly involved in lipofuscinogenesis accumulation of bcl 2 may reflect a mechanism for counterbalancing ros mediated damage or it might represent the impairment of bcl 2 dependent protection from ros.  
7841373bcl 2bcl 21.0lipofuscin|proto oncogene proteins|proto oncogene proteins c bcl 2|gtp binding proteins|  
8922414bcl 2bcl 21.0the importance of ros in programmed cell death also has been suggested from the neuroprotective effects of bcl 2 family proteins which seem to act by inhibiting ros induced cell damage kane et al. 1993 ; zhong et al. 1993 ; myers et al. 1995 ; lawrence et al. 1996 .  
10671549bcl 2bcl 21.0we linked decreased susceptibility of the wt cells to higher and more stable bcl 2 and decreased reactive oxygen species.  
10671549bcl 2bcl 21.0furthermore g93a cells showed a significant decrease of bcl 2 expression and as target of no derived radicals showed lower cytochrome c oxidase activity.  
10671549bcl 2bcl 21.0among these the protein product of bcl 2 protooncogene plays a pivotal role in apoptosis by regulating cytochrome c efflux from mitochondria which in turn activates cysteine proteases caspases ultimately leading to specific dna fragmentatio 
10671549bcl 2bcl 21.0constitutive expression of high bcl 2 protein levels by transfection experiments has proven that bcl 2 or related family members can protect from no mediated apoptosis 15 16 .  
10671549bcl 2bcl 21.0the results obtained showed that gsno mediated apoptosis in these cells is associated with a canonical sequence of events including bcl 2 p53 and p21 modulation cytochrome c release in the cytosol and caspase 3 activation.  
10671549bcl 2bcl 21.0se inhibitor mixture dithiothreitol dtt sulfanilamide p aminobenzenesulfonamide phenylmethylsulfonyl fluoride n 1 naphthyl ethylenediamine dihydrochloride bathocuproinedisulfonic acid monoclonal anti bcl 2 clone bcl 2 100 monoclonal anti p53 clone bp53 12 and cytochrome c horse heart were obtained from sigma.  
10671549bcl 2bcl 21.0 clone bcl 2 100 monoclonal anti p53 clone bp53 12 and cytochrome c horse heart were obtained from sigma.  
10671549bcl 2bcl 21.0p53 p21 and bcl 2 proteins detection cell pellet was resuspended in lysis buffer containing 10 m m tris/hcl ph 7.4 5 m m edta 150 m m nacl 0.5% octyphenoxy polyethoxyethanol igepal ca 630 sigma and protease inhibitors 
10671549bcl 2bcl 21.0sates were then centrifuged at 14 000 _amp_#215; g for 15 min at 4 degreec and supernatants were removed and stored at 80 degreec. 50 microg of proteins were loaded on a 10 for p53 or 12% for p21 and bcl 2 polyacrylamide gel.  
10671549bcl 2bcl 21.0monoclonal anti bcl 2 1:5000 monoclonal anti p53 1:5000 or polyclonal anti p21 1:500 was used as primary antibodies.  
10671549bcl 2bcl 21.0an alternative model for protein export from mitochondria depends on bax and/or bid two members of the bcl 2 protein family 57 .  
10671549bcl 2bcl 21.0in our experiments bcl 2 was down regulated by the gsno treatment in sh sy5y cells whereas the resistance of wt cells to apoptosis was associated with a higher level of this protein in the treated cells.  
10671549bcl 2bcl 21.0since they were the most prone to no induced apoptosis we propose a causative role for bcl 2 in the increased susceptibility of g93a cells to apoptosis.  
10671549bcl 2bcl 21.0it has been suggested that the antiapoptotic effects of bcl 2 be at least in part due to its antioxidant activity 59 .  
10671549bcl 2bcl 21.0t known it is established that the cytosolic steady state of reactive oxygen species which are potentially threatening species and modulators of physiological signal transduction 60 is increased when bcl 2 is down regulated.  
10671549bcl 2bcl 21.0a vicious circle including down regulation of bcl 2 and deviating redox activity of copper in the g93a mutant may be the amplification factor leading to ros unbalance in g93a cells and may explain how and why an als mutant cause a pro apoptotic respon 
10671549bcl 2bcl 21.0bcl 2 content of sh sy5y cells and effects on it by cu zn sod and gsno treatment.  
10671549bcl 2bcl 21.0bcl 2 immunoreactive protein was detected by western blotting using a monoclonal antibody as described under "experimental procedures." 50 microg protein of cell extracts was loaded on each lane.  
10671549bcl 2bcl21.0apoptotic markers: cytochrome c release caspase activation p53 accumulation p21 increase and bcl2 down regulation to examine the sequence of events occurring upon gsno toxicity we measured some of the molecular markers of apoptotic cell death at 48 h from the apoptogenic stimulus.  
10671549bcl 2bcl 21.0bcl 2 protein modulation is responsible for cell survival or suicide; constitutive expression of high bcl 2 protein levels by transfection experiments has proven that bcl 2 or related family members can protect cells from no mediated apoptosis 44 45 .  
10671549bcl 2bcl 21.0in our experiments as evidenced by western blot analysis untreated sh sy5y and wt cells express high levels of bcl 2 protein whereas g93a cells show a much lower content fig 4 . 48 h of gsno treatment decreased bcl 2 expression although to a different extent; in particular bcl 2 content of g93a cells was at the lim 
10671549bcl 2bcl 21.0 protein whereas g93a cells show a much lower content fig 4 . 48 h of gsno treatment decreased bcl 2 expression although to a different extent; in particular bcl 2 content of g93a cells was at the limit of detection.  
10671549bcl 2bcl 21.0cytochrome c group|nitroso compounds|proto oncogene proteins c bcl 2|tumor suppressor protein p53|nitric oxide|s nitrosoglutathione|glutathione|superoxide dismutase|caspases|oncogene protein p2|  
11050436bcl 2bcl 21.0in transgenic mice bearing cuznsod mutations known to cause als in humans the protective bcl 2 protein when overexpressed transgenically can protect against neuronal death brought about by als mutations in experimental animals [ 37 and 38 ].  
11679167bcl 2bcl 21.0several proteins have been identified as being major regulators of apoptosis including the bcl 2 family and caspases.  
11679167bcl 2bcl 21.0the bcl 2 family of proteins consist of anti apoptotic proteins such as bcl 2 and bcl x l and pro apoptotic proteins such as bax and bak gross et al. 1999 .  
11679167bcl 2bcl 21.0on dna strand breaks and plasma membrane inversion laun et al. 2001 ; v the life span of non dividing yeast cells lacking superoxide dismutase is extended by overexpressing the anti apoptotic protein bcl 2 longo et al. 1999 .  
11679167bcl 2bcl 21.0the regulatory role of the bcl 2 members e.g. depends on their ability to regulate the mitochondrial function.  
11679167bcl 2bcl 21.0in yeast bcl 2 proteins interact with the voltage dependent anion channel vdac and the adenine nucleotide translocator ant and these proteins are components of the mitochondrial permeability transition pore complex 
12392777bcl 2bcl 21.0moreover nf _amp_#x3ba;b induces the expression of the so called inhibitor of apoptosis proteins iaps bcl 2 and calbindins [ 179 and 270 ].  
14739060bcl 2bcl21.0three main signals cause the release of apoptogenic mitochondrial mediators: _amp_#x2022; pro apoptotic members of bcl2 family _amp_#x2022; elevated levels of intra cellular calcium such as that triggered by excitotoxicity _amp_#x2022; elevated levels of ros_amp_#x2013;rns  
15850589bcl 2bcl21.0treatment with inhibitors of mptp opening and overexpression of bcl2 which inhibits the opening of mptp under stressful conditions delayed the disease onset and prolonged survival in transgenic mice with mutant sod1 [42] [43] and [44] and rendered cells transfected wi 
15896810bcl 2bcl 21.0however although activation of stress tolerance signaling leading to protective nuclear responses such as increased expression of heat shock proteins antioxidant enzymes and bcl 2 may be triggered to withstand all the above mentioned pathogenic changes a vicious cycle of increasing oxidative damage may insidiously develop over a period of years inducing progressive degenerativ 
15896810bcl 2bcl 21.0in addition hsp70 binds to and modulates the function of bag 1 the bcl 2 binding protein [142] thus modulating some type of apoptosis related cell death.  
16046141bcl 2bcl21.0members 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 
16046141bcl 2bcl 21.0pasinelli 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 .  
16050975bcl 2bcl 21.0both inhibition of caspase activation li et al. 2000 and the overexpression of the mitochondrial anti apoptotic protein bcl 2 kostic et al. 1997 slow motor neuron degeneration and extend the survival of sod1 mutant mice.  
16050975bcl 2bcl 21.0an example of such potentially harmful protein protein interactions is the binding of mutant sod1 with bcl 2 pasinelli et al. 2004 .  
16050975bcl 2bcl 21.0within mitochondria mutant sod1 may interfere with the anti apoptotic function of bcl 2 pasinelli et al. 2004 affect mitochondrial import by interfering with the translocation machinery tom/tim liu et al. 2004 generate toxic free radicals ros via aberrant superoxide chemistry estevez et 
16242643bcl 2bcl 21.0in addition malonate induced down regulation of the antiapoptotic gene bcl 2 was not prevented by minocycline controversially the mechanism previously proposed to explain minocycline protective action.  
16242643bcl 2bcl 21.0among them the down regulation of caspases and inos and the up regulation of bcl 2 have been documented recently wang et al. 2004 .  
16242643bcl 2bcl 21.0in order to check whether these pathways were involved in malonate induced granular cell death we first analyzed the pattern of expression of inos caspase 3 8 and 9 and the antiapoptotic gene bcl 2 in malonate treated cells.  
16242643bcl 2bcl 21.0however 50 mm malonate caused a significant down regulation of the antiapoptotic gene bcl 2 fig 6 b .  
16242643bcl 2bcl 21.0therefore we studied whether minocycline would prevent the down regulation of bcl 2 gene expression induced by malonate.  
16242643bcl 2bcl 21.0as depicted in fig. 6 b minocycline consistently with its lack of protective effect failed to block the down regulation of bcl 2 caused by malonate.  
16242643bcl 2bcl 21.0additionally although malonate treatment fails to induce the mrna expression of caspase 3 8 and 9 as well as inos it decreases the mrna of the antiapoptotic protein bcl 2 an effect that was not abrogated by minocycline.  
16242643bcl 2bcl 21.0conversely we did find a significant down regulation of bcl 2 expression after a 24 h malonate exposure.  
16242643bcl 2bcl 21.0it should be noted that the up regulation of bcl 2 gene expression has been recently proposed as a mechanism mediating minocycline induced cytoprotection wang et al. 2004 .  
16242643bcl 2bcl 21.0however abounding on the lack of protective effect by minocycline in the present work this drug failed to reverse the down regulation of bcl 2 induced by malonate treatment nor induced bcl 2 expression by itself.  
16242643bcl 2bcl 21.0fig. 6._amp_#xa0;malonate does not affect inos caspase 3 8 and 9 but significantly reduces bcl 2 mrna expression levels. mrna expression in malonate treated cerebellar granular cells was quantitatively measured by real time pcr using gadph mrna levels as control.  
16242643bcl 2bcl 21.0 b effect of malonate on bcl 2 mrna expression levels.  
16242643bcl 2bcl 21.0minocycline pre treatment fails to avoid the bcl 2 down regulation induced by malonate.  
16242643bcl 2bcl 21.0cardiolipins|enzyme inhibitors|malonates|neuroprotective agents|neurotoxins|proto oncogene proteins c bcl 2|reactive oxygen species|minocycline|malonic acid|glutathione|succinate dehydrogenase|caspases|  
16624679bcl 2bcl 21.0interestingly bcl 2 which has protective activity against oxidative stress [24] and prevents cell death induced by rotenone by blocking the loss of mitochondrial membrane potential [45] and [49] was trapped by sod1 aggr 
16624679bcl 2bcl 21.0other putative components of this complex are the peripheral benzodiazepine receptor pbr creatine kinase ck hexokinase ii hk cyclophilin d cyp d and bax/bcl 2 like proteins bax bak bcl 2 .  
17105868bcl 2bcl 21.0the ratio of apoptotic cell death genes bax to bcl 2 is increased at both the mrna and protein level in spinal motor neurons from patients with als and from sod1 g93a mice mu et al. 1996 ; vukosavic et al. 1999 .  
17105868bcl 2bcl 21.0mutant sod1 g93a has been observed to aggregate in spinal cord mitochondria but not liver mitochondria and binds to bcl 2 pasinelli et al. 2004 .  
17105868bcl 2bcl 21.0altered expression and dysfunction of bcl 2 may contribute to the activation of mitochondrial apoptosis machinery such as caspase 9 caspase 3 and cytochrome c in spinal motor neurons of als transgenic mice and humans with als guegan et al. 200 
17105868bcl 2bcl 21.0in support of this idea overexpression of bcl 2 or the caspase inhibitory protein xiap prolongs survival and improves motor performance in als mice expressing the sod1 g93a mutation kostic et al. 1997 ; inoue et al. 2003 .  
17105868bcl 2bcl 21.0the latter effect may be attributable to interaction of mutant sod1 and bcl 2 causing mitochondrial dysfunction and subsequently increased sensitivity to oxidative stress pasinelli et al. 2004 .  
17496232bcl 2bcl 21.0increased no and onoo result in dna damage p53 accumulation increased bax/bcl 2 cytochrome c cyt c release and caspase activation.  
17496232bcl 2bcl 21.0some antiapoptotic effects include s nitrosylation and inhibition of caspases increase of hsps and bcl 2 and activation of akt/pkb which induces cytoprotective gene expression through nf kappab activation 85 .  
17496232bcl 2bcl 21.0on the other hand proapoptotic effects of no include inhibition of nf kappab decreased bcl 2 expression 87 89 118 and increased p53 expression both by no mediated inhibition of proteasome degradation and by direct dna damage.  
17496232bcl 2bcl 21.0caspases are cysteine proteases that cleave specific aspartate residues in other regulatory proteins like bcl 2 bax and mekk for review see ref 83 .  
17496232bcl 2bcl 21.0disruption of the nf kappab gene is associated with embryo lethality; many antiapoptotic pathways like bcl 2 are induced by nf kappab.