Release of mitochondrial cytochrome c is upstream of caspase activation in chemical-induced apoptosis in human monocytic tumour cells

1998 ◽  
Vol 102-103 ◽  
pp. 121-129 ◽  
Author(s):  
Jianguo Zhuang ◽  
Gerald M Cohen
Keyword(s):  
Cytochrome C ◽  
Tumour Cells ◽  
Mitochondrial Cytochrome ◽  
Caspase Activation ◽  
Induced Apoptosis ◽  
Mitochondrial Cytochrome C

Cytochrome c release into cytosol with subsequent caspase activation during warm ischemia in rat liver

2001 ◽  
Vol 281 (4) ◽  
pp. G1115-G1123 ◽  
Author(s):  
Junpei Soeda ◽  
Shinichi Miyagawa ◽  
Kenji Sano ◽  
Junya Masumoto ◽  
Shun'Ichiro Taniguchi ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Warm Ischemia ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Dependent Manner ◽  
Mitochondrial Cytochrome ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Apoptotic Pathway ◽  
Mitochondrial Cytochrome C

Apoptosis plays an important role in liver ischemia and reperfusion (I/R) injury. However, the molecular basis of apoptosis in I/R injury is poorly understood. The aims of this study were to ascertain when and how apoptotic signal transduction occurs in I/R injury. The apoptotic pathway in rats undergoing 90 min of warm ischemia with reperfusion was compared with that of rats undergoing prolonged ischemia alone. During ischemia, mitochondrial cytochrome c was released into the cytosol in a time-dependent manner in hepatocytes and sinusoidal endothelial cells, and caspase-3 and an inhibitor of caspase-activated DNase were cleaved. However, apoptotic manifestation and DNA fragmentation were not observed. After reperfusion, nuclear condensation, cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling, and DNA fragmentation were observed and caspase-8 and Bid cleavage occurred. In contrast, prolonged ischemia alone induced necrosis rather than apoptosis. In summary, our results show that release of mitochondrial cytochrome c and caspase activation proceed during ischemia, although apoptosis is manifested after reperfusion.

scholarly journals Bcr-Abl-Mediated Protection from Apoptosis Downstream of Mitochondrial Cytochrome c Release

2004 ◽  
Vol 24 (23) ◽  
pp. 10289-10299 ◽  
Author(s):  
Paula B. Deming ◽  
Zachary T. Schafer ◽  
Jessica S. Tashker ◽  
Malia B. Potts ◽  
Mohanish Deshmukh ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Mitochondrial Cytochrome ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Intact Cells ◽  
Caspase Recruitment Domain ◽  
Distinct Mechanism ◽  
Mitochondrial Cytochrome C

ABSTRACT Bcr-Abl, activated in chronic myelogenous leukemias, is a potent cell death inhibitor. Previous reports have shown that Bcr-Abl prevents apoptosis through inhibition of mitochondrial cytochrome c release. We report here that Bcr-Abl also inhibits caspase activation after the release of cytochrome c. Bcr-Abl inhibited caspase activation by cytochrome c added to cell-free lysates and prevented apoptosis when cytochrome c was microinjected into intact cells. Bcr-Abl acted posttranslationally to prevent the cytochrome c-induced binding of Apaf-1 to procaspase 9. Although Bcr-Abl prevented interaction of endogenous Apaf-1 with the recombinant prodomain of caspase 9, it did not affect the association of endogenous caspase 9 with the isolated Apaf-1 caspase recruitment domain (CARD) or Apaf-1 lacking WD-40 repeats. These data suggest that Apaf-1 recruitment of caspase 9 is faulty in the presence of Bcr-Abl and that cytochrome c/dATP-induced exposure of the Apaf-1 CARD is likely defective. These data provide a novel locus of Bcr-Abl antiapoptotic action and suggest a distinct mechanism of apoptosomal inhibition.

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