title: Inhibition of the leptin-induced activation of the p38 MAPK pathway contributes to the protective effects of naringin against high glucose-induced injury in H9c2 cardiac cells.
abstract: Leptin, a product of the obese gene, has been reported to contribute to the development of cardiomyocyte hypertrophy in patients with diabetes and to activate the p38 mitogen-activated protein kinase (MAPK) pathway in cardiomyocytes. In this study, we demonstrate that naringin, a citrus flavonone, protects cardiomyoblasts (H9c2 cells) against high glucose (HG)-induced apoptosis by modulating the activation of the p38 MAPK pathway. We investigated the hypothesis that naringin prevents HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway in H9c2 cells. Our results demonstrated that the exposure of H9c2 cells to HG (35 mmol/l) for a 24 h markedly upregulated the expression levels of both leptin and leptin receptors. However, the increase in the expression levels of leptin and leptin receptors was greatly attenuated by treatment of the H9c2 cells with 80 µmol/l naringin 2 h prior to exposure to HG. In addition, treatment of the cells with 50 ng/ml leptin antagonist (LA) for 24 h prior to exposure to HG markedly ameliorated the increased expression of phosphorylated (p)-p38 MAPK induced by HG. Of note, pre-treatment of the cells with either 80 µmol/l naringin or 50 ng/ml LA markedly inhibited the HG-induced injury, leading to an increase in cell viability and a decrease in the total number of apoptotic cells, preventing reactive oxygen species (ROS) generation, as well as the dissipation of mitochondrial membrane potential (MMP). In conclusion, the findings of the present study provide the first evidence that the leptin-induced activation of the p38 MAPK pathway is involved in HG-induced injury, including cytotoxicity, apoptosis, ROS generation and the dissipation of MMP in H9c2 cardiac cells. Our data demonstrate that naringin protects cardiac cells against HG-induced injury by inhibiting the leptin-induced activation of the p38 MAPK pathway.
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Jingfu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Mo
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Runmin
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Ruina
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Cardiovasology, The Affiliated Hospital, Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Keng
authors.initials: K
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects; D044950:Flavanones / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity; D006801:Humans; D020738:Leptin / Q000378:metabolism; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D044950:Flavanones; D020738:Leptin; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C005274:naringin