Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats.
The aim of this study was to investigate the effect of sirtinol, as an inhibitor of sirtuin NAD-dependent histone deacetylases, on myocardial ischemia reperfusion injury following early and late ischemia preconditioning (IPC). Rats underwent sustained ischemia and reperfusion (IR) alone or proceeded by early or late IPC. Sirtinol (S) was administered before IPC. Arrhythmias were evaluated based on the Lambeth model. Infarct size (IS) was measured using triphenyltetrazolium chloride staining. The transcription level of antioxidant-coding genes was assessed by real-time PCR. In early and late IPC groups, IS and the number of arrhythmia were significantly decreased (P < 0.05 and P < 0.01 vs IR, respectively). In S + early IPC, incidences of arrhythmia and IS were not different compared with the early IPC group. However, in S + late IPC the IS was different from the late IPC group (P < 0.05). In late IPC but not early IPC, transcription levels of catalase (P < 0.01) and Mn-SOD (P < 0.05) increased, although this upregulation was not significant in the S + late IPC group. Our results are consistent with the notion that different mechanisms are responsible for early and late IPC. In addition, sirtuin NAD-dependent histone deacetylases may be implicated in late IPC-induced cardioprotection.
Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.|School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Fereshteh
F
Safari
Department of Physiology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran.
Shahnaz
S
Shekarforoosh
Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Tahmineh
T
Hashemi
Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
Simin
S
Namvar Aghdash
Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Asefeh
A
Fekri
Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. sa.physiol@gmail.com.|Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. sa.physiol@gmail.com.
Fatemeh
F
Safari
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D001549:Benzamides / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D009284:Naphthols / Q000494:pharmacology*; D017208:Rats, Wistar; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D056565:Sirtuin 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D009284:Naphthols; C097475:Sirt2 protein, rat; C439060:sirtinol; D002374:Catalase; D013482:Superoxide Dismutase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D056565:Sirtuin 2
Early ischemia preconditioning; Late ischemia preconditioning; Myocardial ischemia reperfusion; Sirtinol; Sirtuin1; Sirtuin2
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