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Impairment of the activity of the xenobiotic‐metabolizing enzymes arylamine N ‐acetyltransferases 1 and 2 (NAT1/NAT2) by peroxynitrite in mouse skeletal muscle cells
Author(s) -
Dairou Julien,
Dupret Jean-Marie,
Rodrigues-Lima Fernando
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.07.043
Subject(s) - acetyltransferases , peroxynitrite , enzyme , biochemistry , xenobiotic , chemistry , skeletal muscle , arylamine n acetyltransferase , isozyme , biology , acetylation , endocrinology , gene , superoxide
Reactive nitrogen species and their by‐products, such as peroxynitrite, modulate many physiological functions of skeletal muscle. Peroxynitrite generation occuring under specific conditions, such as inflammation, may also lead to skeletal muscle dysfunction and pathologies. Arylamine N ‐acetyltransferases (NATs) are xenobiotic‐metabolizing enzymes (XMEs) involved in the detoxification and/or metabolic activation of several drugs and chemicals. In addition to other XMEs, such as gluthatione S ‐transferases or cytochromes P450, NAT enzymes are expressed in skeletal muscle. We show here that functional NAT1 and NAT2 isoforms are expressed in mouse myotubes and that peroxynitrite may impair their activity in these cells. We show that this inactivation is likely due to the irreversible modification of NATs catalytic cysteine residue in vivo. Our results suggest that peroxynitrite‐dependent inactivation of muscle XMEs such as NATs may contribute to muscle dysfunction by impairing the biotransformation activity of this key cellular defense enzyme system.