title: Inducible nitric oxide synthase (NOS2) expressed in septic patients is nitrated on selected tyrosine residues: implications for enzymic activity.
abstract: Tyrosine nitration is a post-translational protein modification with potentially significant biological implications. In the present study we demonstrate, for the first time, that tyrosine residues of human inducible nitric oxide synthase (NOS2) can be nitrated by peroxynitrite in vitro, leading to a decreased activity. Moreover, we show that NOS2 expressed in a skeletal muscle from septic patients is nitrated on selective tyrosine residues belonging to a canonic sequence. This phenomenon could be an endogenous mechanism of in vivo modulation of NOS2 enzymic activity.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U408 and IFR 02, Faculté X. Bichat, 75018 Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lanone
authors.forename: Philippe
authors.initials: P
authors.lastname: Manivet
authors.forename: Jacques
authors.initials: J
authors.lastname: Callebert
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D009566:Nitrates / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011487:Protein Conformation; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D018805:Sepsis / Q000201:enzymology*; D018411:Spodoptera; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D009566:Nitrates; D011994:Recombinant Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat