cPKC gamma Inhibits Caspase-9-Initiated Neuronal Apoptosis in an Ischemia Reperfusion Model In Vitro Through p38 MAPK-p90RSK-Bad Pathway

摘要

Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase C gamma (cPKC gamma) plays neuroprotective role in ischemic strokes. Further, we found that cPKC gamma knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKC gamma-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKC gamma knockdown remarkably increased neuronal death after OGD. We also found that cPKC gamma knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKC gamma could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKC gamma knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKC gamma knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKC gamma partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.