Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Alan D. Guerrero
Tanzania
Research Article
Promotion of Caspase Activation by Caspase-9-mediated Feedback Amplification of Mitochondrial Damage
Author(s): Alan D. Guerrero, Ingo Schmitz, Min Chen and Jin WangAlan D. Guerrero, Ingo Schmitz, Min Chen and Jin Wang
Mitochondrial disruption during apoptosis results in the activation of caspase-9 and a downstream caspase cascade. Triggering this caspase cascade leads to the cleavage of anti-apoptotic Bcl-2 family proteins, resulting in feedback amplification of mitochondrial disruption. However, whether such a feedback loop plays an important role in the promotion of caspase activation and execution of apoptosis has not been well established. We observed that mutated Bcl-2 or Bcl-xL that are resistant to cleavage by caspases inhibited caspase-9-induced caspase activation in human H9 T cells. The release of Smac after the activation of caspase-9 was also inhibited by cleavage-resistant Bcl-2 or Bcl-xL. Consistently, caspase-9-deficient cells were defective in the release of Smac after induction of apoptosis. Moreover, addition of a Smac mimetic overcame the inhibitory effects of cleavage-resistant .. View More»
DOI:
10.4172/2155-9899.1000126