SIRT1 is a redox‐sensitive deacetylase that is post‐translationally modified by oxidants and carbonyl stress

• DOI: 10.1096/fj.09-151308
• Publication Date: 2010-04-13T02:28:20Z
• Authors: Samuel Caito; Saravanan Rajendr...; Suzanne Cook; Sangwoon Chung; Hongwei Yao; Alan E. Friedman; Paul S. Brookes; Irfan Rahman
• Keywords: Acrolein; Cytoprotection; Protein Carbonylation

Sirtuinl (SIRT1) deacetylase levels are decreased in chronic inflammatory conditions and aging where oxidative stress occurs. We determined the mechanism of SIRT1 redox post-translational modifications leading to its degradation. Human lung epithelial cells exposed hydrogen peroxide (150–250 µM), aldehyde-acrolein (10–30 cigarette smoke extract (CSE;0.1–1.5%) presence intracellular glutathione-modulating agents at 1–24 h, were assayed cells, as well lungs mice lacking overexpressing glutaredoxin-1 (Glrx1), wild-type (WT) response (CS). CSE aldehydes dose time dependently protein levels, with EC50 1% for 30 µM acrolein 6 >80% inhibition 24 h CSE, which was regulated by modulation thiol status cells. CS WT mice, enhanced deficiency Glrx1 prevented overexpression Glrx1. Oxidants, aldehydes, induced carbonyl on cysteine residues concomitant activity. Proteomics studies revealed alkylation residue SIRT1. Our data suggest that oxidants/aldehydes covalently modify SIRT1, decreasing enzymatic activity marking proteasomal degradation, has implications conditions.—Caito, S., Rajendrasozhan, Cook, Chung, Yao, H., Friedman, A. E., Brookes, P. Rahman, I. is a redox-sensitive post-translationally modified oxidants stress. FASEB J. 24, 3145–3159 (2010). www.fasebj.org