Anti-apoptotic action of hydrogen sulfide is associated with early JNK inhibition.
The mechanism of action of Hydrogen sulfide (H(2)S) as a novel endogenous gaseous messenger and potential cardioprotectant is not fully understood. We therefore investigated the prevention of cardiomyocyte apoptosis by exogenous H(2)S 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 0.5h during reperfusion. NaHS (H(2)S donor) significantly inhibited the early phosphorylation of JNK, especially at 0.5h. 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 1h after reperfusion, the inhibition of apoptosis by H(2)S was negated. In conclusion, this is novel evidence that early JNK inhibition during reperfusion is associated with H(2)S-mediated protection against cardiomyocyte apoptosis.
Shi
Sa
S
Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. shisa1976@hotmail.com
Li
Qing-song
QS
Li
Hong
H
Zhang
Li
L
Xu
Man
M
Cheng
Jia-li
JL
Peng
Cheng-hai
CH
Xu
Chang-qing
CQ
Tian
Ye
Y
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000378:metabolism; D019610:Cytoprotection; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
D000873:Anthracenes; C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D006862:Hydrogen Sulfide