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SIRT 2 mediates NADH ‐induced increases in Nrf2, GCL , and glutathione by modulating Akt phosphorylation in PC 12 cells
Author(s) -
Cao Wei,
Hong Yunyi,
Chen Heyu,
Wu Fan,
Wei Xunbin,
Ying Weihai
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12236
Subject(s) - sirt2 , phosphorylation , glutathione , protein kinase b , microbiology and biotechnology , chemistry , oxidative phosphorylation , biochemistry , biology , sirtuin , nad+ kinase , enzyme
SIRT 2 plays important roles in multiple biological processes. It is unclear whether SIRT 2 affects antioxidant capacity by modulating Nrf2, a key transcription factor for multiple antioxidant genes. By studying NADH ‐treated differentiated PC 12 cells, we found that NADH induced a significant increase in the nuclear Nrf2, which was prevented by both SIRT 2 si RNA and SIRT 2 inhibitor, AGK 2. SIRT 2 si RNA also blocked the NADH ‐induced increases in glutamate cysteine ligase ( GCL ) and glutathione. Moreover, SIRT 2 si RNA and AGK 2 blocked NADH ‐induced Akt phosphorylation, and inhibition of Akt phosphorylation prevented NADH ‐induced increases in the nuclear Nrf2 and glutathione. Collectively, our study shows that SIRT 2 regulates nuclear Nrf2 levels by modulating Akt phosphorylation, thus modulating the levels of GCL and total glutathione.