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 micro mol/l produced tyrosine nitration and inactivation of GS, whereas 50 micro 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 micro mol/l). Further, a putative "denitrase" activity restored the activity of peroxynitrite (5 micro 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.
Görg
Boris
B
Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, D-40225 Dusseldorf, Germany.
Qvartskhava
Natalia
N
Voss
Peter
P
Grune
Tilman
T
Häussinger
Dieter
D
Schliess
Freimut
F
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000737:chemistry / Q000378:metabolism*; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012756:Sheep; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D009566:Nitrates; D030421:Peroxynitrous Acid; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex; D005974:Glutamate-Ammonia Ligase