Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression
- Department of Internal Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 1608582 (Japan)
NAD{sup +}-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), H{sub 2}O{sub 2}. Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H{sub 2}O{sub 2}, Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H{sub 2}O{sub 2}-induced apoptosis through the upregulation of catalase. H{sub 2}O{sub 2} induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H{sub 2}O{sub 2}-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.
- OSTI ID:
- 21143766
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 372, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2008.04.176; PII: S0006-291X(08)00853-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
SIRT1 overexpression decreases cisplatin-induced acetylation of NF-{kappa}B p65 subunit and cytotoxicity in renal proximal tubule cells
miR-543 promotes gastric cancer cell proliferation by targeting SIRT1