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

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume372
Issue number1
DOIs
Publication statusPublished - 2008 Jul 18

Fingerprint

Oxidative stress
Catalase
Oxidative Stress
Apoptosis
Kidney
Reactive Oxygen Species
Cells
Cell Survival
Up-Regulation
Forkhead Transcription Factors
Gene Silencing
NAD
Down-Regulation
Genes
Cell Line

Keywords

  • Apoptosis
  • Catalase
  • Forkhead transcription factor
  • FoxO3a
  • Histone deacetylase
  • Oxidative stress
  • Renal proximal tubular cell
  • Renal tubular cell
  • ROS
  • Sirt1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression. / Hasegawa, Kazuhiro; Wakino, Shu; Yoshioka, Kyoko; Tatematsu, Satoru; Hara, Yoshikazu; Minakuchi, Hitoshi; Washida, Naoki; Tokuyama, Hirobumi; Hayashi, Koichi; Itoh, Hiroshi.

In: Biochemical and Biophysical Research Communications, Vol. 372, No. 1, 18.07.2008, p. 51-56.

Research output: Contribution to journalArticle

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AU - Hara, Yoshikazu

AU - Minakuchi, Hitoshi

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