Regulation of caspase-3 activity by insulin in skeletal muscle cells involves both PI3-kinase and MEK-1/2

摘要: A hallmark of skeletal muscle atrophy is increased activities several proteolytic systems, including caspase-3. We have previously shown that conditions involving insulin deficiency or resistance increase both overall protein degradation and caspase-3-mediated actin cleavage. In the present experiments, we examined how regulates caspase-3 activity in L6 myotubes. Reducing serum concentration culture media from 2 to 0.5% overnight Addition proteolytically active cells attenuated responses within 4 h. Individually, inhibitors either phosphatidylinositide 3-kinase (PI3K) MEK1/2 partially blocked insulin-induced reduction activity; combination, completely prevented attenuating activity. Insulin suppressed by a complex mechanism included direct inhibition due an interaction between cellular inhibitor apoptosis-1 indirect via phosphorylation (i.e., inactivation) proapoptotic Bad, which participates intrinsic mitochondrial) apoptosis activation cascade. Unlike other cell types, Bad Ser112 was mediated PI3K/Akt pathway rather than MEK/ERK/ribosomal S6 kinase pathway. summary, our findings indicate multistep process unique muscle, thus providing insights about muscle-specific nature process.