Adaptation to hydrogen peroxide in Saccharomyces cerevisiae: The role of NADPH-generating systems and the SKN7 transcription factor

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• 作者：Chong-Han Ng ; Shi-Xiong Tan ; Gabriel G. Perrone ; Geoffrey W. Thorpe ; Vincent J. Higgins ; Ian W. Dawes
• 关键词：Adaptive response ; Oxidative stress ; Hydrogen peroxide ; Transcription factors ; NADPH generation ; Glutathione ; Cellular redox
• 刊名：Free Radical Biology and Medicine
• 出版年：2008
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 March 2008
• 卷：44
• 期：6
• 页码：1131-1145
• 文件大小：2174 K

摘要

A total of 286 Hb>2b>Ob>2b>-sensitive Saccharomyces cerevisiae deletion mutants were screened to identify genes involved in cellular adaptation to Hb>2b>Ob>2b> stress. YAP1, SKN7, GAL11, RPE1, TKL1, IDP1, SLA1, and PET8 were important for adaptation to Hb>2b>Ob>2b>. The mutants were divisible into two groups based on their responses to a brief acute dose of Hb>2b>Ob>2b> and to chronic exposure to Hb>2b>Ob>2b>. Transcription factors Yap1p, Skn7p, and Gal11p were important for both acute and chronic responses to Hb>2b>Ob>2b>. Yap1p and Skn7p were acting in concert for adaptation, which indicates that upregulation of antioxidant functions rather than generation of NADPH or glutathione is important for adaptation. Deletion of GPX3 and YBP1 involved in sensing Hb>2b>Ob>2b> and activating Yap1p affected adaptation but to a lesser extent than YAP1 deletion. NADPH generation was also required for adaptation. RPE1, TKL1, or IDP1 deletants affected in NADPH production were chronically sensitive to Hb>2b>Ob>2b> but resistant to an acute dose, and other mutants affected in NADPH generation tested were similarly affected in adaptation. These mutants overproduced reduced glutathione (GSH) but maintained normal cellular redox homeostasis. This overproduction of GSH was not regulated at transcription of the gene encoding b3;-glutamylcysteine synthetase.