Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression

Kazuhiro Hasegawa, Shu Wakino, Kyoko Yoshioka, Satoru Tatematsu, Yoshikazu Hara, Hitoshi Minakuchi, Naoki Washida, Hirobumi Tokuyama, Koichi Hayashi, Hiroshi Itoh

研究成果: Article

155 引用 (Scopus)

抜粋

NAD+-dependent protein deacetylase Sirt1 regulates cellular apoptosis. We examined the role of Sirt1 in renal tubular cell apoptosis by using HK-2 cells, proximal tubular cell lines with or without reactive oxygen species (ROS), H2O2. Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H2O2, Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H2O2-induced apoptosis through the upregulation of catalase. H2O2 induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H2O2-induced apoptosis. In conclusion, endogenous Sirt1 maintains cell survival by regulating catalase expression and by preventing the depletion of ROS required for cell survival. In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels.

元の言語English
ページ(範囲)51-56
ページ数6
ジャーナルBiochemical and Biophysical Research Communications
372
発行部数1
DOI
出版物ステータスPublished - 2008 7 18

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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