Reversible inhibition of mammalian glutamine synthetase by tyrosine nitration

The effect of tyrosine nitration on mammalian GS activity and stability was studied in vitro. Peroxynitrite at a concentration of 5 mu mol/l produced tyrosine nitration and inactivation of GS, whereas 50 mu mol/l peroxynitrite additionally increased S-nitrosylation and carbonylation and degradation of GS by the 20S proteasome. (-)Epicatechin completely prevented both, tyrosine nitration and inactivation of GS by peroxynitrite (5 mu mol/l). Further, a putative "denitrase" activity restored the activity of peroxynitrite (5 mu mol/l)-treated GS. The data point to a potential regulation of GS activity by a reversible tyrosine nitration. High levels of oxidative stress may irreversibly damage and predispose the enzyme to proteasomal degradation. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.