Methionine sulfoxide reductase A attenuates heme oxygenase-1 induction through inhibition of Nrf2 activation

作者：Kim Jung Yeon; Choi Seung Hee; Lee Eujin; Kang Young Jin; Kim Hwa Young^*

来源：Archives of Biochemistry and Biophysics, 2012, 528(2): 134-140.

DOI：10.1016/j.abb.2012.09.012

• Methionine sulfoxide reductase
• MsrA
• Heme oxygenase-1
• Nrf2
• Cell proliferation
• p21

Methionine sulfoxide reductase A (MsrA) functions as a protein repair enzyme by catalyzing the stereospecific reduction of methionine-S-sulfoxide to methionine. We previously identified that MsrA deficiency inhibits normal cell growth via activation of the p53-p21 pathway. In this study, we report a critical role of MsrA in expression of heme oxygenase-1 (HO-1), a highly inducible enzyme that has an anti-proliferative effect mediated by up-regulation of p21. Down-regulation of MsrA induced HO-1 expression in mammalian cells with increased p21 levels, but MsrA overexpression did not affect HO-1 expression. MsrA depletion activated Nrf2 by increasing its expression and nuclear translocation. Nrf2 activation was associated with increased reactive oxygen species production. MsrA overexpression in MsrA-depleted cells led to the reduction of increased HO-1 expression, and suppressed nuclear accumulation of Nrf2. Taken together, the data suggest that MsrA attenuates HO-1 induction by inhibiting Nrf2 activation.

• 出版日期2012-12-15