4.5 Article

Nitric oxide and dihydrolipoic acid modulate the activity of caspase 3 in HepG2 cells

Journal

FEBS LETTERS
Volume 583, Issue 21, Pages 3525-3530

Publisher

WILEY
DOI: 10.1016/j.febslet.2009.10.016

Keywords

Lipoic acid; Caspase; Nitric oxide; Dihydrolipoic; Denitrosation

Funding

  1. NIH [GM044100]
  2. Walter Reed Army Institute of Research [W81XWH-09-P-0631, W81XWH-06-1-0247]
  3. Office of Naval Research [42237]

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Herein, we report that dihydrolipoic acid and lipoic acid (LA) plus lipoamide dehydrogenase and NADH denitrosate S-nitrosocaspase 3 (CASP-SNO). In HepG2 cells, S-nitroso-L-cysteine ethyl ester (SNCEE) impeded the activity of caspase 3 (CASP-SH), while a subsequent incubation of the cells in SNCEE-free medium resulted in endogenous denitrosation and reactivation of CASP-SH. The latter process was inhibited in thioredoxin reductase-deficient HepG2 cells, in which, however, LA markedly reactivated CASP-SH. The data obtained are discussed with focus on low molecular mass dithiols that mimic the activity of thioredoxin in reactions of protein S-denitrosation. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

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