SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury |
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| Affiliation: | 1. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi''an 710032, China;2. Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi''an 710032, China;3. Department of Thoracic and Cardiovascular Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing 210008, Jiangsu, China;4. Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi''an 710038, China;5. Department of Aerospace Medicine, The Fourth Military Medical University, Xi''an 710032, China;6. Department of Geriatrics, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi''an 710032, China;1. Department of Anesthesiology, University Hospital Split, Split, Croatia;2. Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Split, Croatia;1. Department of Cardiology, Xi''an No.3 Hospital, Faculty of Life Sciences and Medicine, Northwest University, Xi''an, China;2. Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi''an, China;3. Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi''an, China;4. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, Xi''an, China;5. Department of Cardiothoracic Surgery, Central Theater Command General Hospital of Chinese People''s Liberation Army, Wuhan, China |
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| 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. |
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| Keywords: | Ischemia reperfusion Curcumin SIRT1 signaling Mitochondrial oxidative damage Cardioprotection |
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