Methionine sulfoxide reductase A attenuates heme oxygenase-1 induction through inhibition of Nrf2 activation
- Methionine sulfoxide reductase A attenuates heme oxygenase-1 induction through inhibition of Nrf2 activation
- 김화영; 김정연; 최승희; 이유진; 강영진
- OXIDATIVE STRESS; ANTIOXIDANT RESPONSE; MOLECULAR-MECHANISMS; CONFERS RESISTANCE; CELLS; OVEREXPRESSION; PROLIFERATION; EXPRESSION; PROTECTS; P21
- Issue Date
- ELSEVIER SCIENCE INC
- ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, v.528, no.2, pp.134 - 140
- 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. (C) 2012 Elsevier Inc. All rights reserved.
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