title: Exogenous ARC down-regulates caspase-3 expression and inhibits apoptosis of broiler chicken cardiomyocytes exposed to hydrogen peroxide.
abstract: Apoptosis repressor with caspase recruitment domain (ARC) is highly involved in apoptosis induced by oxidative stress or ischaemia/reperfusion injury. Furthermore, even though the exact mechanism is still unknown, some studies suggest that exogenous ARC also possesses anti-apoptotic ability. The study investigated whether mouse-derived ARC acquires anti-apoptotic ability and the pathway of regulation in chick embryo cardiomyocytes. To evaluate whether mouse-derived ARC can inhibit chick embryo cardiomyocyte apoptosis induced by hydrogen peroxide, recombinant pcDNA3.1/ARC plasmid was acquired and transfected into chick embryo cardiomyocytes. ARC-related gene (caspase-2, caspase-8, caspase-3, and caspase-9, cytochrome C, bcl-2, and XIAP) mRNA and protein expression levels were detected by real-time polymerase chain reaction and western blotting, respectively. Here we demonstrate that hydrogen peroxide induced apoptosis in chick embryo cardiomyocytes in a time-dependent manner and that this effect could be suppressed by mouse-derived ARC expression. Moreover, unlike endogenous ARC, exogenous ARC was exclusively expressed in the cytoplasm and down-regulated caspase-2, caspase-8, and caspase-3, bcl-2, and XIAP gene expression levels. However, only caspase-3 protein levels were decreased. In addition, threonine 149 phosphorylation by CK2 was required for exogenous ARC to exert an anti-apoptotic effect in chicken embryo cardiomyocytes and suggested exogenous ARC may in part share the same pathway of regulation with endogenous ARC. These results indicate that mouse-derived ARC plays an important role in protection of chick embryo cardiomyocytes against oxidative stress apoptosis by inhibiting caspase-3 mRNA and protein expression levels.
authors: Department of Veterinary Internal Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P.R. China.
authors: Liming
authors: L
authors: Wu
authors: Zhaofang
authors: Z
authors: Xi
authors: Rui
authors: R
authors: Guo
authors: Songrui
authors: S
authors: Liu
authors: Shijin
authors: S
authors: Yang
authors: Dongyang
authors: D
authors: Liu
authors: Shiqi
authors: S
authors: Dong
authors: Dingzong
authors: D
authors: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015723:Gene Library; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D009124:Muscle Proteins; C491787:Nol3 protein, mouse; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D053148:Caspase 3