title: Cyclooxygenase-2 mediates the delayed cardioprotection induced by hydrogen sulfide preconditioning in isolated rat cardiomyocytes.
abstract: 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.
authors: Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors: Li-Fang
authors: LF
authors: Hu
authors: Ting-Ting
authors: TT
authors: Pan
authors: Kay Li
authors: KL
authors: Neo
authors: Qian Chen
authors: QC
authors: Yong
authors: Jin-Song
authors: JS
authors: Bian
mesh_terms: 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
chemical_list: 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