期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1843, 期 12, 页码 2926-2936出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2014.09.002
关键词
Skeletal muscle; Differentiation; Apoptosis; Mitochondrion; Cytochrome c; XIAP
资金
- Natural Sciences and Engineering Research Council of Canada [341256]
Skeletal muscle differentiation requires activity of the apoptotic protease caspase-3. We attempted to identify the source of caspase activation in differentiating C2C12 skeletal myoblasts. In addition to caspase-3, caspase-2 was transiently activated during differentiation; however, no changes were observed in caspase-8 or -9 activity. Although mitochondrial Bax increased, this was matched by Bcl-2, resulting in no change to the mitochondrial Bax:Bcl-2 ratio early during differentiation. Interestingly, mitochondrial membrane potential increased on a timeline similar to caspase activation and was accompanied by an immediate, temporary reduction in cytosolic Smac and cytochrome c. Since XIAP protein expression dramatically declined during myogenesis, we investigated whether this contributes to caspase-3 activation. Despite reducing caspase-3 activity by up to 57%, differentiation was unaffected in cells overexpressing normal or E3-mutant XIAP. Furthermore, a XIAP mutant which can inhibit caspase-9 but not caspase-3 did not reduce caspase-3 activity or affect differentiation. Administering a chemical caspase-3 inhibitor demonstrated that complete enzyme inhibition was required to impair myogenesis. These results suggest that neither mitochondria] apoptotic signaling nor XIAP degradation is responsible for transient caspase-3 activation during C2C12 differentiation. (C) 2014 Elsevier B.V. All rights reserved.
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