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Role of AMPK in cardioprotection by leptin-preconditioning
렙틴 전처치에 의한 심장보호기전에서 AMPK의 역할

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Authors
김기석
Advisor
호원경
Major
의과대학 의학과
Issue Date
2014-02
Publisher
서울대학교 대학원
Description
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2014. 2. 호원경.
Abstract
Introduction: Leptin, a product of the ob gene, is a 16-kDa peptide synthesized primarily by white adipose tissue. It is also produced in the heart, suggesting that it has a cardioprotective effect. AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a key role in cardioprotection in the abnormal heart. However, it is not clear whether AMPK-mediated cardioprotection influences the effects of leptin in cardiac muscle. Here, I investigated the mechanism of cardioprotection in leptin preconditioning and the relationship between leptin preconditioning-induced cardioprotection and the regulation of AMPK.
Methods: A rat ischemia model was constructed using left anterior descending coronary artery occlusion (CAO). Infarct size was measured to evaluate the cardioprotective effect. A rat cardiac myoblast cell line (H9c2) was used to investigate the cardioprotective mechanism of leptin.
Results: Leptin decreased myocardial infarct size in rat cardiac ischemic reperfusion model. The effect of leptin was abolished in combination with compound C, an AMPK inhibitor or NAC, a ROS scavenger. Leptin phosphorylated AMPK dose- and time-dependently in H9c2 cells. Leptin also induced generation of reactive oxygen species (ROS) dose- and time-dependently in H9c2 cells. AMPK phosphorylation by leptin was abolished in combination with NAC, however, leptin-induced ROS generation was not affected by compound C. Therefore, Leptin induced generation of ROS followed by activation of AMPK. Activated AMPK decreased cardiac ischemic damage.
Conclusions: AMPK activation plays a key role in leptin preconditioning-induced cardioprotection. Leptin-induced ROS generation results in AMPK activation.
Language
English
URI
https://hdl.handle.net/10371/121944
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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