title: Genistein suppresses the isoproterenol-treated H9c2 cardiomyoblast cell apoptosis associated with P-38, Erk1/2, JNK, and NFκB signaling protein activation.
abstract: Heart disease (HD) is associated with estrogen and therefore gender and menopausal status. In addition, clinical evidence shows that increased serum norepinephrine is found in patients with HD. Therefore, this study aimed to investigate the cardio-protective effect of genistein, a selective estrogen receptor modulator (SERM) from soy bean extract, in H9c2 cardiomyoblast cells treated with isoproterenol (ISO), a norepinephrine analog. In this in vitro model, image data and results from western blotting shown that ISO treatment was capable of inducing cellular apoptosis, especially the mitochondrial dependent pathway. Treatment of genistein could suppress the expression of mitochondrial pro-apoptotic proteins including Bad, caspase-8, caspase-9, and caspase-3 in H9c2 treated with ISO. By contrast, several survival proteins were expressed in H9c2 treated with genistein, such as phosphor (p)-Akt, p-Bad, and p-Erk1/2. Furthermore, we confirmed that the protective role of genistein was partially mediated through the expression of Erk1/2, Akt, and NF κ B proteins by adding several pathway inhibitors. These in vitro data suggest that genistein may be a safe and natural SERM alternative to hormone therapy in cardio-protection.
authors.affiliation: Division of Cardiology, Taipei Medical University, Shuang-Ho Hospital, Taipei, Taiwan , Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Syun
authors.initials: WS
authors.lastname: Hu
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Li
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Cecilia Hsuan
authors.initials: CH
authors.lastname: Day
authors.forename: Tung-Sheng
authors.initials: TS
authors.lastname: Chen
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D002316:Cardiotonic Agents; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D004967:Estrogens / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology* / Q000627:therapeutic use; D006331:Heart Diseases / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D007545:Isoproterenol / Q000009:adverse effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000235:genetics* / Q000502:physiology*; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000502:physiology; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics* / Q000502:physiology; D008517:Phytotherapy; D051381:Rats; D020845:Selective Estrogen Receptor Modulators; D013025:Glycine max; D015854:Up-Regulation / Q000187:drug effects*; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000502:physiology
chemical_list: C494821:Bad protein, rat; D002316:Cardiotonic Agents; D004967:Estrogens; D016328:NF-kappa B; D020845:Selective Estrogen Receptor Modulators; D051025:bcl-Associated Death Protein; D019833:Genistein; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D007545:Isoproterenol