title: SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury.
abstract: Ischemia reperfusion (IR) injury (IRI) is harmful to the cardiovascular system and causes mitochondrial oxidative stress. Silent information regulator 1 (SIRT1), a type of histone deacetylase, contributes to IRI. Curcumin (Cur) is a strong natural antioxidant and is the active component in Curcuma longa; Cur has protective effects against IRI and may regulate the activity of SIRT1. This study was designed to investigate the protective effect of Cur pretreatment on myocardial IRI and to elucidate this potential mechanism. Isolated and in vivo rat hearts and cultured neonatal rat cardiomyocytes were subjected to IR. Prior to this procedure, the hearts or cardiomyocytes were exposed to Cur in the absence or presence of the SIRT1 inhibitor sirtinol or SIRT1 siRNA. Cur conferred a cardioprotective effect, as shown by improved postischemic cardiac function, decreased myocardial infarct size, decreased myocardial apoptotic index, and several biochemical parameters, including the up-regulation of the antiapoptotic protein Bcl2 and the down-regulation of the proapoptotic protein Bax. Sirtinol and SIRT1 siRNA each blocked the Cur-mediated cardioprotection by inhibiting SIRT1 signaling. Cur also resulted in a well-preserved mitochondrial redox potential, significantly elevated mitochondrial superoxide dismutase activity, and decreased formation of mitochondrial hydrogen peroxide and malondialdehyde. These observations indicated that the IR-induced mitochondrial oxidative damage was remarkably attenuated. However, this Cur-elevated mitochondrial function was reversed by sirtinol or SIRT1 siRNA treatment. In summary, our results demonstrate that Cur pretreatment attenuates IRI by reducing IR-induced mitochondrial oxidative damage through the activation of SIRT1 signaling.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Weixun
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Scientific Research, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, 145 Changle West Road, Xi'an 710032, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address: shiqiangyu210@126.com.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address: dinghuayi210@126.com.
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yi
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China. Electronic address: zhenxiaojin210@126.com.
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D003474:Curcumin
keywords: AAR; CF; CK; COX; Cardioprotection; Cur; Curcumin; FOXO1; HR; IPC; IR; IRI; Ischemia reperfusion; LDH; LVDP; MDA; Mitochondrial oxidative damage; SDH; SIR; SIRT1; SIRT1 signaling; SOD; TTC; acetylated-forkhead box O1; area at risk; coronary flow; creatinine kinase; curcumin; cytochrome c oxidase; heart rate; ischemia reperfusion; ischemia reperfusion injury; ischemic preconditioning; lactate dehydrogenase; methane dicarboxylic aldehyde; silent information regulator 1; simulated ischemia reperfusion; succinate dehydrogenase; super oxygen dehydrogenases; the left ventricular developed pressure; triphenyltetrazolium chloride