title: HSP25 down-regulation enhanced p53 acetylation by dissociation of SIRT1 from p53 in doxorubicin-induced H9c2 cell apoptosis.
abstract: Heat shock proteins (HSPs) play important roles in cellular stress resistance. Previous reports had already suggested that HSP27 played multiple roles in preventing doxorubicin-induced cardiotoxicity. Although HSP25 might have biological functions similar to its human homolog HSP27, the mechanism of HSP25 is still unclear in doxorubicin-induced cardiomyocyte apoptosis. To investigate HSP25 biological function on doxorubicin-induced apoptosis, flow cytometry was employed to analyze cell apoptosis in over-expressing HSP25 H9c2 cells in presence of doxorubicin. Unexpectedly, the H9c2 cells of over-expressing HSP25 have no protective effect on doxorubicin-induced apoptosis. Moreover, no detectable interactions were detected by coimmunoprecipitation between HSP25 and cytochrome c, and HSP25 over-expression failed in preventing cytochrome c release induced by doxorubicin. However, down-regulation of endogenous HSP25 by a specific small hairpin RNA aggravates apoptosis in H9c2 cells. Subsequent studies found that HSP25, but not HSP90, HSP70, and HSP20, interacted with SIRT1. Knockdown of HSP25 decreased the interaction between SIRT1 and p53, leading to increased p53 acetylation on K379, up-regulated pro-apoptotic Bax protein expression, induced cytochrome c release, and triggered caspase-3 and caspase-9 activation. These findings indicated a novel mechanism by which HSP25 regulated p53 acetylation through dissociation of SIRT1 from p53 in doxorubicin-induced H9c2 cell apoptosis.
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.|Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.|Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Shunlin
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.|Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Kangkai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Meidong
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Huali
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China. xiaoxianzhong@csu.edu.cn.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D045304:Cytochromes c; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Cardiomyocyte apoptosis; Doxorubicin-induced cardiotoxicity; HSP25; SIRT1; p53