title: Ibutilide protects against cardiomyocytes injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways.
abstract: Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid atrial activation and atrial structural remodeling. The contribution of endoplasmic reticulum and mitochondria stress to AF has been highlighted. As the class III antiarrhythmic agent, ibutilide are widely used to AF. This study was designed to explore whether ibutilide could treat AF by inhibiting endoplasmic reticulum stress pathways and mitochondria stress. The neonatal rat cardiomyocytes were isolated and exposed to H2O2, ibutilide was add to the culture medium 12 h. Then the cell viability, oxidative stress levels and apoptotic rate were analyzed. In addition, endoplasmic reticulum stress related protein (GRP78, GRP94, CHOP), mitochondria-dependent protein (Bax, Bcl-2) and caspase-3/9/12 were identified by real-time PCR and western blot analysis. In our results, remarkable decreased cell viability and oxidative stress levels were detected in cardiomyocytes after treating with H2O2. The apoptotic rate and the expression of proteins involved in mitochondrial stress and endoplasmic reticulum stress pathways increased. While ibutilide significantly inhibited these changes. These data suggested that ibutilide serves a protective role against H2O2-induced apoptosis of neonatal rat cardiomyocytes, and the mechanism is related to suppression of mitochondrial stress and endoplasmic reticulum stress.
authors.affiliation: Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, No. 22 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China.
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Huang
authors.affiliation: Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, No. 22 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China. weichengxi1224@163.com.
authors.forename: Cheng-Xi
authors.initials: CX
authors.lastname: Wei
authors.affiliation: Affiliated Hospital of Inner Mongolia University for Nationalities, No. 1472 Holin He Street, Tongliao, Inner Mongolia, 028002, People's Republic of China. langzhe73@163.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D016877:Oxidants; D020011:Protective Agents; D013449:Sulfonamides; C067192:ibutilide; D006861:Hydrogen Peroxide
keywords: Atial fibrillation; Endoplasmic reticulum stress; Ibutilide; Mitochondrial stress; Oxidative stress