title: Apolipoprotein-J prevents angiotensin II-induced apoptosis in neonatal rat ventricular cells.
abstract: BACKGROUND
  Up-regulation of angiotensin II (AngII) occurs in cardiac diseases, such as congestive heart failure, cardiac hypertrophy, myocardial ischemia and atrial fibrillation, which represent major health problems. Evidence from in vivo studies suggests that the level of Apolipoprotein-J (ApoJ) is also elevated but plays a protective role in cardiovascular disease. This study aimed to evaluate the protective effects of ApoJ against cytotoxicity of AngII in neonatal rat ventricular cells (NRVCs).
  
  
  RESULTS
  In culture, NRVCs were damaged by exposure to AngII, and ApoJ overexpression using an adenovirus vector significantly reduced the AngII-induced cell injury. ApoJ also prevented AngII from augmenting Nox2/gp91(phox) expression. The reactive oxygen species (ROS) scavenger, Mn(III)TBAP, showed similar results of attenuating AngII-induced cell damage. Furthermore, ApoJ overexpression increased phosphorylation of Akt, and the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 diminished the antioxidant effects of ApoJ, and prevented the protective effect of ApoJ against the cytotoxicity of AngII. Moreover, upregulation of nuclear factor κB (NF-κB) p65 expression and phosphorylation of p38 mitogen-activated protein kinase (MAPK) mediated by AngII in cultured NRVCs were significantly inhibited by overexpression of ApoJ. The p38 MAPK inhibitor SB203580 and the NF-κB inhibitor PDTC protected NRVCs from injury caused by AngII.
  
  
  CONCLUSIONS
  ApoJ serves as a cytoprotective protein in NRVCs against cytotoxicity of AngII through the PI3K-Akt-ROS and MAPK/ NF-κB pathways.
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. 297400148@qq.com.
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. 1311263248@qq.com.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Kong
authors.affiliation: Health and Medical Development Research Center of Hebei Province, Shijiazhuang, Hebei, China. 569483621@qq.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Nan
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. qsy304@sohu.com.
authors.forename: Shuying
authors.initials: S
authors.lastname: Qi
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. sjzrls@163.com.
authors.forename: Leisheng
authors.initials: L
authors.lastname: Ru
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. dingch2001@sohu.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Cardiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, China. slwangdm@126.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051152:Clusterin / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D065840:Protective Factors; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: C498500:Clu protein, rat; D051152:Clusterin; D016328:NF-kappa B; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases