Anti-apoptotic action of hydrogen sulfide is associated with early JNK inhibition

The mechanism of action of Hydrogen sulfide (H₂S) as a novel endogenous gaseous messenger and potential cardioprotectant is not fully understood. We therefore investigated the prevention of cardiomyocyte apoptosis by exogenous H₂S and the signaling pathways leading to cardioprotection. Using a simulated ischemia–reperfusion (I/Re) model with primary cultured rat neonatal cardiomyocytes, I/Re induced a rapid, time-dependent phosphorylation of c-Jun N-terminal kinase (JNK), with significant elevation at 0.25 h and a peak at 0.5 h during reperfusion. NaHS (H₂S donor) significantly inhibited the early phosphorylation of JNK, especially at 0.5 h. Both NaHS and SP600125 (specific JNK inhibitor) decreased the number of apoptotic cells, lowered cytochrome C release and enhanced Bcl-2 expression. When NaHS application was delayed 1 h after reperfusion, the inhibition of apoptosis by H₂S was negated. In conclusion, this is novel evidence that early JNK inhibition during reperfusion is associated with H₂S-mediated protection against cardiomyocyte apoptosis.