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Leptin protects H9c2 rat cardiomyocytes from H 2 O 2 ‐induced apoptosis
Author(s) -
Eguchi Megumi,
Liu Yuantao,
Shin EyunJung,
Sweeney Gary
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06465.x
Subject(s) - leptin , apoptosis , medicine , endocrinology , phosphatidylserine , annexin , cytochrome c , chemistry , microbiology and biotechnology , biology , obesity , biochemistry , membrane , phospholipid
Obesity is a known risk factor for induction of myocardial infarction, but, paradoxically, may also confer a protective effect against subsequent remodeling leading to heart failure. In this study, we investigated the effect of leptin, the product of the obese ( ob ) gene, on cardiomyocyte apoptosis, a well‐characterized component of cardiac remodeling after myocardial infarction. Exposing H9c2 cells to H 2 O 2 decreased cell viability, and this was attenuated by pretreating cells with leptin for 1 h, but not 24 h. Leptin also attenuated the ability of H 2 O 2 to increase phosphatidylserine exposure and annexin V binding. Further investigation of underlying mechanisms of leptin’s protective effect demonstrated that the H 2 O 2 ‐induced decrease in mitochondrial membrane potential (Ψ) leading to cytochrome c release was attenuated by leptin pretreatment, and this was associated with reduced translocation of the pro‐apoptotic Bax protein to the mitochondrial membrane. Finally, leptin prevented H 2 O 2 ‐induced increases in caspase‐3 cleavage and activity, although again 24 h leptin pretreatment did not confer significant protection. In summary, we have demonstrated that acute leptin pretreatment mediates anti‐apoptotic effects in H9c2 rat cardiomyocytes, which may be of significance in clarifying the direct impact of leptin on the heart.