首页|Pharmacological postconditioning with sappanone A ameliorates myocardial ischemia reperfusion injury and mitochondrial dysfunction via AMPK-mediated mitochondrial quality control
Pharmacological postconditioning with sappanone A ameliorates myocardial ischemia reperfusion injury and mitochondrial dysfunction via AMPK-mediated mitochondrial quality control
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NSTL
Elsevier
Pharmacological postconditioning (PPC), drug intervention before or during the early minutes of reperfusion, could stimulate cardioprotection as ischemic postconditioning. In this study, we examined whether PPC with sappanone A (SA), a homoisoflavanone with potent antioxidant and anti-inflammatory activity, has a protective effect on myocardial ischemia reperfusion injury (MIRI), and explored the underlying mechanism. A MIRI model was established using the Langendorff method. After 30 min of ischemia, isolated rat hearts were treated with SA at the onset of reperfusion to stimulate PPC. The changes in myocardial infarct size, mitochondrial function, mitochondrial biogenesis, mitophagy, and mitochondrial fission and fusion were detected. The results showed that SA postconditioning decreased the myocardial infarct size, inhibited the release of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and cardiac troponin (cTnI), as well as improved cardiac function, enhanced myocardial ATP content and mitochondrial complex activity, and prevented the loss of mitochondrial membrane potential and opening of mitochondrial permeability transition pore (mPTP). Mechanistically, we found that SA was an AMP-activated protein kinase (AMPK) activator, and SA postconditioning could facilitate mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) copy number and the expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1 alpha). In addition, it balanced mitochondrial dynamics by decreasing fission and increasing fusion, and enhanced mitophagy in an AMPK-dependent manner. Moreover, AMPK silencing abolished the cardioprotection of SA postconditioning. Collectively, our study demonstrated that SA postconditioning ameliorated MIRI and mitochondrial dysfunction by regulation of mitochondrial quality control via activating AMPK. This finding provides a new insight into pharmacological action and clinical use of SA.
Myocardial ischemia reperfusion injuryPharmacological postconditioningSappanone AMitochondrial quality controlAMP-activated protein kinase
Shi, Xiaojing、Li, Yang、Wang, Yaguang、Ding, Tiejia、Zhang, Xiaowen、Wu, Nan
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Jinzhou Med Univ, Dept Cardiol, Affiliated Hosp 1, Jinzhou, Peoples R China
China Med Univ, Med Res Ctr, Shengjing Hosp, 36 Sanhao St, Shenyang 110004, Peoples R China
China Med Univ, Cent Lab, Affiliated Hosp 1, 155th North Nanjing St, Shenyang 110001, Liaoning
NSTL
Elsevier
