title: Endophilin A2 protects H2O2-induced apoptosis by blockade of Bax translocation in rat basilar artery smooth muscle cells.
abstract: BACKGROUND
  Apoptosis plays a central role in maintaining the normal cell number and tissue homeostasis. Endophilins are a family of evolutionarily conserved proteins that have the critical role in endocytosis. Here, we determined whether endophilin A2 (EndoII) contributes to hydrogen peroxide (H2O2)-induced apoptosis in rat basilar artery smooth muscle cells (BASMCs) and the underlying mechanisms.
  
  
  RESULTS
  By using small interference RNA (siRNA) and EndoII overexpression strategy, we found that EndoII siRNA knockdown reduced cell viability and promoted H2O2-induced cell apoptosis, evidenced by loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase (PARP). In contrast, EndoII overexpression showed opposite effects and inhibited H2O2-induced BASMCs apoptosis. Further studies revealed that there was a direct interaction between EndoII and Bax. Upon H2O2-induced apoptosis, the association of EndoII with Bax were significantly decreased, while the interaction of Bax/tBid were increased, accompanied by a translocation of Bax from cytosol to mitochondria. Knockdown of EndoII did not affect the expression of Bax, but further promoted the binding of Bax with tBid and favored the accumulation of Bax to mitochondria as well as Bax activation; whereas EndoII overexpression produced the opposite effects. In addition, EndoII siRNA aggravated, but EndoII overexpression alleviated, the reduction of Bcl-2 expression in H2O2-treated cells.
  
  
  CONCLUSIONS
  These data suggested a role of EndoII in protecting BASMCs apoptosis induced by H2O2, possibly by inhibiting the addressing of Bax to mitochondria. Targeting on EndoII may be a new strategy to treat apoptosis-associated diseases.
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China; Department of Pharmacolgy, Guangzhou Medical University, Guangzhou, 510182, China.
authors: Yun
authors: Y
authors: Liu
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China.
authors: Min
authors: M
authors: Gao
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China.
authors: Ming-Ming
authors: MM
authors: Ma
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China.
authors: Yong-Bo
authors: YB
authors: Tang
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China.
authors: Jia-Guo
authors: JG
authors: Zhou
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China.
authors: Guan-Lei
authors: GL
authors: Wang
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China. Electronic address: duyanhua@mail.sysu.edu.cn.
authors: Yan-Hua
authors: YH
authors: Du
authors: Department of Pharmacology, Cardiac & Cerebral Vascular Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510089, China. Electronic address: guanyy@mail.sysu.edu.cn.
authors: Yong-Yuan
authors: YY
authors: Guan
mesh_terms: D000217:Acyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001488:Basilar Artery / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C494828:Bax protein, rat; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase
keywords: Bax; EndophilinA2; Hydrogen peroxide; Mitochondrial apoptosis; Smooth muscle cells