Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes.
We previously reported that hydrogen sulfide (H(2)S) preconditioning (SP) produces cardioprotection in isolated rat cardiomyocytes. The present study was designed to determine the involvement of cyclooxygenase-2 (COX-2) in the SP-induced delayed cardioprotection. Isolated cardiac myocytes were treated with NaHS (100 microM, a H(2)S donor) for 30 min and then cultured for 20 h followed by ischemia/reperfusion insults. SP significantly increased cell viability, percentage of rod-shaped cells, and myocyte contractility after 10 min of reperfusion. Given 30 min before and during lethal ischemia, two selective COX-2 inhibitors, NS-398 and celebrex, abrogated SP-induced cardioprotective effects. Moreover, SP upregulated the expression of COX-2 and increased PGE(2) production in the cardiac myocytes. These effects were significantly attenuated by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker, and chelerythrine, a selective protein kinase C (PKC) inhibitor, suggesting that activation of both K(ATP) and PKC is required for the stimulation of COX-2. Additionally, NG-nitro-L: -arginine methyl ester, a nitric oxide synthase inhibitor, failed to regulate COX-2 protein expression but inhibited SP-enhanced COX-2 activity and PGE(2) production. In conclusion, we provided the first evidence that SP may produce delayed cardioprotection via K(ATP)/PKC dependent induction of COX-2 expression and via nitric oxide-induced COX-2 activation.
Hu
Li-Fang
LF
Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Pan
Ting-Ting
TT
Neo
Kay Li
KL
Yong
Qian Chen
QC
Bian
Jin-Song
JS
D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006331:Heart Diseases / Q000201:enzymology / Q000517:prevention & control*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D054086:KATP Channels / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013373:Substance P / Q000494:pharmacology
D000393:Air Pollutants; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D054086:KATP Channels; D020011:Protective Agents; D013373:Substance P; D051546:Cyclooxygenase 2; D053612:Janus Kinases; D011493:Protein Kinase C; D015232:Dinoprostone; D006862:Hydrogen Sulfide