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Publication : Polydatin protects cardiomyocytes against myocardial infarction injury by activating Sirt3.

First Author  Zhang M Year  2017
Journal  Biochim Biophys Acta Volume  1863
Issue  8 Pages  1962-1972
PubMed ID  27613967 Mgi Jnum  J:255685
Mgi Id  MGI:6105358 Doi  10.1016/j.bbadis.2016.09.003
Citation  Zhang M, et al. (2017) Polydatin protects cardiomyocytes against myocardial infarction injury by activating Sirt3. Biochim Biophys Acta 1863(8):1962-1972
abstractText  Myocardial infarction (MI), which is characterized by chamber dilation and left ventricular (LV) dysfunction, represents a major cause of morbidity and mortality worldwide. Polydatin (PD), a monocrystalline and polyphenolic drug isolated from a traditional Chinese herb (Polygonum cuspidatum), alleviates mitochondrial dysfunction. We investigated the effects and underlying mechanisms of PD in post-MI cardiac dysfunction. We constructed an MI model by left anterior descending (LAD) coronary artery ligation using wild-type (WT) and Sirt3 knockout (Sirt3(-/-)) mice. Cardiac function, cardiomyocytes autophagy levels, apoptosis and mitochondria biogenesis in mice that underwent cardiac MI injury were compared between groups. PD significantly improved cardiac function, increased autophagy levels and decreased cardiomyocytes apoptosis after MI. Furthermore, PD improved mitochondrial biogenesis, which is evidenced by increased ATP content, citrate synthase (CS) activity and complexes I/II/III/IV/V activities in the cardiomyocytes subjected to MI injury. Interestingly, Sirt3 knockout abolished the protective effects of PD administration. PD inhibited apoptosis in cultured neonatal mouse ventricular myocytes subjected to hypoxia for 6h to simulate MI injury. PD increased GFP-LC3 puncta, and reduced the accumulation of protein aggresomes and p62 in cardiomyocytes after hypoxia. Interestingly, the knock-down of Sirt3 nullified the PD-induced beneficial effects. Thus, the protective effects of PD are associated with the up-regulation of autophagy and improvement of mitochondrial biogenesis through Sirt3 activity.
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