Deficiency of myeloperoxidase increases infarct volume and nitrotyrosine formation in mouse brain.
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.
Takizawa
Shunya
S
Department of Neurology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
Aratani
Yasuaki
Y
Fukuyama
Naoto
N
Maeda
Nobuyo
N
Hirabayashi
Hisayuki
H
Koyama
Hideki
H
Shinohara
Yukito
Y
Nakazawa
Hiroe
H
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*
D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase