title: Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress.
abstract: Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-Jun N-terminal kinase (JNK), and then triggered apoptotic events. High-dose Hcy also resulted in a decrease in mitochondrial membrane potential (Δψm) and an increase in cytoplasmic cytochrome C and the expression of cleaved caspase-9. Pretreatment of cardiomyocytes with sodium 4-phenylbutyric acid (an ER stress inhibitor) significantly inhibited Hcy-induced apoptosis. Furthermore, blocking the PERK pathway partly alleviated Hcy-induced ER stress-modulated cardiomyocyte apoptosis, and down-regulated the levels of Bax and cleaved caspase-3. Experimental taurine pretreatment inhibited the expression of ER stress-related proteins, and protected against apoptotic events triggered by Hcy-induced ER stress. Taken together, our results suggest that Hcy triggered ER stress in cardiomyocytes, which was the crucial molecular mechanism mediating Hcy-induced cardiomyocyte apoptosis, and the adverse effect of Hcy could be prevented by taurine.
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China. zhaolianyoutd@163.com.
authors.forename: Lianyou
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.|Department of Cardiology, Shaanxi Provincial Chinese Traditional Medicine Hospital, Xi'an, People's Republic of China.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xuanhao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics; D006710:Homocysteine / Q000633:toxicity; D008565:Membrane Proteins / Q000235:genetics; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051381:Rats; D013654:Taurine / Q000008:administration & dosage*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D051702:Activating Transcription Factor 6; D006360:Heat-Shock Proteins; D006710:Homocysteine; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D013654:Taurine; C497113:Atf6 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C486557:Ern2 protein, rat
keywords: Apoptosis; Cardiomyocytes; Endoplasmic reticulum stress; Homocysteine; Taurine