title: Exogenous hydrogen sulfide alleviates high glucose-induced cardiotoxicity via inhibition of leptin signaling in H9c2 cells.
abstract: Hydrogen sulfide (H₂S) protects cardiomyoblasts against high glucose (HG)-induced injury by inhibiting the activation of p38 mitogen-activated protein kinase (MAPK). This study aims to determine whether the leptin-p38 MAPK pathway is involved in HG-induced injury and whether exogenous H2S prevents the HG-induced insult through inhibition of the leptin-p38 MAPK pathway in H9c2 cells. H9c2 cells were treated with 35 mM glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. Cell viability; mitochondrial membrane potential (ΔΨ m); apoptosis; reactive oxygen species (ROS) level; and leptin, leptin receptor, and p38 MAPK expression level were measured by the methods indicated. The results showed pretreatment of H9c2 cells with NaHS before exposure to HG led to an increase in cell viability, decrease in apoptotic cells, ROS generation, and a loss of ΔΨ m. Exposure of H9c2 cells to 35 mM glucose for 24 h significantly upregulated the expression levels of leptin and leptin receptors. The increased expression levels of leptin and leptin receptors were markedly attenuated by pretreatment with 400 μM NaHS. In addition, the HG-induced increase in phosphorylated (p) p38 MAPK expression was ameliorated by pretreatment with 50 ng/ml leptin antagonist. In conclusion, the present study has demonstrated for the first time that the leptin-p38 MAPK pathway contributes to the HG-induced injury in H9c2 cells and that exogenous H₂S protects H9c2 cells against HG-induced injury at least in part by inhibiting the activation of leptin-p38 MAPK pathway.
authors.affiliation: Department of Cardiovasology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People's Republic of China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhuang
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Long
authors.forename: Xiao-Bian
authors.initials: XB
authors.lastname: Dong
authors.forename: Dong-Hong
authors.initials: DH
authors.lastname: Liu
authors.forename: Xin-Xue
authors.initials: XX
authors.lastname: Liao
mesh_terms: D000818:Animals; D066126:Cardiotoxicity / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D020738:Leptin / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020738:Leptin; D020011:Protective Agents; D017382:Reactive Oxygen Species; D054411:Receptors, Leptin; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D006862:Hydrogen Sulfide