title: Endoplasmic reticulum stress and C/EBP homologous protein-induced Bax translocation are involved in angiotensin II-induced apoptosis in cultured neonatal rat cardiomyocytes.
abstract: The aim of this study was to identify the roles and potential mechanisms of endoplasmic reticulum stress (ER stress), proapoptotic transcription factor C/EBP homologous protein (CHOP) and Bax in angiotensin II (Ang II)-induced cardiomyocyte apoptosis. Cultured neonatal rat cardiomyocytes were incubated with Ang II or antisense CHOP oligonucleotide which was used to inhibit CHOP expression. Expressions of ER chaperone immunoglobulin heavy chain-binding protein (BiP), CHOP and cytochrome c were examined by Western blotting. Mitochondrial membrane potential (MMP) was detected by a spectrofluorimeter. Apoptosis was analyzed with flow cytometry. Bax translocation was determined by double-labeling of immunofluorescence and Western blotting. Our results showed that Ang II-induced cardiomyocyte apoptosis was associated with the upregulations of BiP and CHOP, Bax translocation, MMP deplorization and cytochrome c release. These above effects were suppressed by antisense CHOP oligonucleotide. Furthermore, BiP and CHOP expressions, reactive oxygen species (ROS) production and cardiomyocyte apoptosis, which were upregulated by Ang II, were depressed by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. From our results, ROS, ER stress and CHOP-mediated Bax translocation may be involved in Ang II-induced cardiomyocyte apoptosis.
authors.affiliation: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, PR China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Zou
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.forename: Shang-Long
authors.initials: SL
authors.lastname: Yao
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D000098:Acetophenones; D000804:Angiotensin II; D045304:Cytochromes c; D006360:Heat-Shock Proteins; D009249:NADP; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C056165:acetovanillone