title: Palmitate induces H9c2 cell apoptosis by increasing reactive oxygen             species generation and activation of the ERK1/2 signaling pathway.
abstract: Cardiac myocytes undergo apoptosis under conditions of high free fatty acid             concentrations, including palmitate, which is implicated in lipotoxic cardiomyopathy.             However, the underlying mechanisms remain unknown. The aim of the present study             was to understand the role of reactive oxygen species (ROS) production and the             extracellular signal‑regulated kinase 1/2 (ERK1/2) signaling pathway in palmitate‑induced             apoptosis in H9c2 cells. H9c2 cells were exposed to palmitate for 12 h. The effect             on the cell viability of H9c2 cells was evaluated using the 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium             bromide (MTT) assay and cell apoptosis was determined by Hoechst 33342 staining.             Levels of intracellular ROS were determined using a peroxide‑sensitive fluorescent             probe, 2',7'‑dichlorofluorescein diacetate. Protein expression was measured by             western blot analysis. Following treatment with palmitate for 12 h, H9c2 cells             apoptosis was demonstrated as increased brightly condensed chromatin or unclear             fragments by staining with Hoechst 33342, which was associated with increasing             levels of active caspase‑3 and cleaved poly (ADP-ribose) polymerase (PARP). In             this model of treatment with palmitate, H9c2 cell apoptosis correlated with increased             levels of p53 and Bax expression and reduced levels of Bcl-2 expression. Palmitate‑induced             apoptosis was observed to increase levels of intracellular ROS production and             p‑ERK1/2 and decrease p‑Akt significantly. Consistent with these results, palmitate‑induced             apoptosis was attenuated by the ERK1/2 inhibitor, U0126, through partial reduction             of intracellular ROS generation. Collectively, these results indicate that palmitate‑induced             apoptosis in H9c2 cells is mediated by activation of the ERK1/2 signaling pathway             and increased ROS generation.
authors: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Hubai 430060, PR China.
authors: Chuan-Dong
authors: CD
authors: Wei
authors: Yan
authors: Y
authors: Li
authors: Hong-Yun
authors: HY
authors: Zheng
authors: Yong-Qing
authors: YQ
authors: Tong
authors: Wen
authors: W
authors: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010168:Palmitates / Q000633:toxicity*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D002070:Butadienes; D009570:Nitriles; D010168:Palmitates; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C113580:U 0126; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3