Abstract 335: Resveratrol Confers Cardioprotection Against Ischemia/Reperfusion Injury by Inhibition of JNK via AMPK
Introduction: Resveratrol (trans-3, 4’, 5-trihydroxystilbene) is a naturally occurring polyphenolic compound found in grapes, fruits and root of plant Polygonum cuspidatum. It modulates ROS generation, energy metabolism and cell death. We hypothesized that resveratrol cardioprotection against ischemia/reperfusion is regulated by free radicals scavenging activities, inhibition of JNK and activation of AMPK.
Methods: Primary chick embryonic ventricular cardiomyocytes (4-5 days old) were exposed to1 h simulated ischemia and 3 h reperfusion. Free radical scavenging capacity of resveratrol was analyzed using electron spin resonance spectrometry for 1-diphenyl-2picrylhydrazyl (DPPH), superoxide and hydroxyl radical. Viability was assessed by propidium iodide uptake (PI) and LDH release. Intracellular ROS was measured by 2’, 7’-dichlorofluorescin diacetate (DCF). Phosphorylation of JNK and AMPK were analyzed by western blot. Resveratrol (50 μM) was given at reperfusion and JNK inhibitor (SP600125, 10 μM), AMPK inhibitor (compound C, 40 μM) and activator (AICAR) were given 1h prior to ischemia.
Results: Resveratrol possessed the scavenging capacity of DPPH, superoxide and hydroxyl radical with weaker effect on hydroxyl radical. Compared to control, it decreased PI staining (26.8 ± 2.6 vs. 46.0 ± 2.6 %, P < 0.01), LDH release and DCF fluorescence (3.2 ± 0.4 vs. 12.4 ± 2.3 a.u., P < 0.05). Resveratrol attenuated JNK phosphorylation and increased AMPK phosphorylation. Further, Compound C enhanced PI staining while AICAR reducing it.
Conclusions: Resveratrol protected cardiomyocytes against ischemia/reperfusion injury by attenuating ROS production, LDH release and cell death. This protection is mediated by activation of AMPK thereby JNK inhibition.
Author Disclosures: H. Huang: None. C. Li: None. Z. Shao: None. J. Yin: None. J. Li: None. T. Vanden Hoek: None.
- © 2014 by American Heart Association, Inc.