ウツギサワ タイジユ   UTSUGISAWA Taiju
  槍澤 大樹
   所属   医学部 医学科(東京女子医科大学病院)
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Candesartan prevents angiotensin II-induced facilitation of hypoxic neuronal damage through PKCdelta inhibition.
掲載誌名 正式名:Brain research. Molecular brain research
略  称:Brain Res Mol Brain Res
ISSNコード:0169328X/0169328X
掲載区分国外
巻・号・頁 135(1-2),pp.134-140
著者・共著者 Utsugisawa Kimiaki, Nagane Yuriko, Utsugisawa Taiju, Obara Daiji, Terayama Yasuo
発行年月 2005/04
概要 To investigate the role of protein kinase Cdelta (PKCdelta) in angiotensin II-induced facilitation mechanisms of hypoxic neuronal damage and whether candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we performed in vitro experiments which were free from vascular components using PC12 cells under hypoxic (12 h)/reoxygenation (0-48 h) conditions. Angiotensin II apparently increased the basal expression level of PKCdelta phosphorylated at Ser(643) before hypoxia, promoted the cleavage of PKCdelta to its catalytic fragment, and fostered the progression of DNA fragmentation after hypoxia. Candesartan inhibited both phosphorylation and cleavage of PKCdelta and suppressed the angiotensin II-induced facilitation of DNA fragmentation under hypoxic/reoxygenation conditions. However, PD123319, an AT2 receptor antagonist, influenced neither PKCdelta nor the angiotensin II-induced facilitation of DNA fragmentation. Furthermore, in PC12 cells expressing the ATP-binding mutant of PKCdelta (PKCdelta(K376R)) acting as a dominant-negative protein, both phosphorylation and cleavage of PKCdelta were attenuated and DNA fragmentation was markedly suppressed regardless of the presence of angiotensin II. These findings suggest that angiotensin II-induced facilitation of DNA fragmentation under hypoxic conditions is mediated by PKCdelta, and the mechanisms can be suppressed by the candesartan mediated blockade of the AT1 receptor.
DOI 10.1016/j.molbrainres.2004.12.004
PMID 15857676