title: Deficiency of myeloperoxidase increases infarct volume and nitrotyrosine formation in mouse brain.
abstract: Peroxynitrite is responsible for nitration in vivo, whereas myeloperoxidase can also catalyze protein nitration in the presence of high NO2(-) levels. Recent reports of myeloperoxidase-mediated enzyme inactivation or lipid peroxidation have suggested a role of myeloperoxidase in various pathological conditions. To clarify the role of myeloperoxidase in ischemic brain injury, the authors measured nitrotyrosine formation and infarct volume in myeloperoxidase-deficient or wild-type mice subjected to 2-hour focal cerebral ischemia-reperfusion. Twenty-four hours after reperfusion, infarct volume was significantly larger in myeloperoxidase-deficient mice than in wild-type mice (81 +/- 20 mm(3) vs. 52 +/- 13 mm(3), P < 0.01), and nitrotyrosine levels in the infarct region were higher in myeloperoxidase-deficient mice than in wild-type mice (13.4 +/- 6.1 microg/mg vs. 9.8 +/- 4.4 microg/mg, P = 0.13). Fourteen hours after reperfusion, the nitrotyrosine level was significantly higher in myeloperoxidase-deficient mice than in wild-type mice (3.3 +/- 2.9 microg/mg vs. 1.4 +/- 0.4 microg/mg, P < 0.05). The authors conclude that the absence of myeloperoxidase increases ischemic neuronal damage in vivo, and that the myeloperoxidase-mediated pathway is not responsible for the nitration reaction in cerebral ischemia-reperfusion.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Aratani
authors.forename: Naoto
authors.initials: N
authors.lastname: Fukuyama
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Hirabayashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Koyama
authors.forename: Yukito
authors.initials: Y
authors.lastname: Shinohara
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D020520:Brain Infarction / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009195:Peroxidase / Q000172:deficiency / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis*
chemical_list: D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase