AMPK Contributes to Cardioprotective Effects of Pterostilbene Against Myocardial Ischemia- Reperfusion Injury in Diabetic Rats by Suppressing Cardiac Oxidative Stress and Apoptosis

Autor: Sanjay Singh, Dan Yan, Yin Cai, Michael G. Irwin, Vidya Kandula, Hong Zheng, Chunyan Wang, Zhengyuan Xia, Ramoji Kosuru, Yalan Li
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
AMPK
Pterostilbene
Physiology
Apoptosis
AMP-Activated Protein Kinases
Pharmacology
medicine.disease_cause
lcsh:Physiology
Rats
Sprague-Dawley
chemistry.chemical_compound
Stilbenes
Creatine Kinase
MB Form
Myocytes
Cardiac
lcsh:QD415-436
Phosphorylation
Cells
Cultured
bcl-2-Associated X Protein
Cardioprotection
lcsh:QP1-981
Caspase 3
Diabetes
Coronary Vessels
Cell Hypoxia
Proto-Oncogene Proteins c-bcl-2
medicine.symptom
medicine.drug
Myocardial Reperfusion Injury
Streptozocin
Diabetes Mellitus
Experimental
lcsh:Biochemistry
03 medical and health sciences
Diabetes mellitus
medicine
Animals
L-Lactate Dehydrogenase
business.industry
Hypoxia (medical)
medicine.disease
Streptozotocin
Rats
Oxidative Stress
Glucose
030104 developmental biology
chemistry
Myocardial ischemia-reperfusion
Reactive Oxygen Species
business
Reperfusion injury
Oxidative stress
Zdroj: Cellular Physiology and Biochemistry, Vol 46, Iss 4, Pp 1381-1397 (2018)
ISSN: 1421-9778
1015-8987
Popis: Background/Aims: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. Methods: Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabetic rats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). Results: PT significantly reduced post-ischemic cardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabetic rats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. Conclusion: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.
Databáze: OpenAIRE
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