Myeloperoxidase has directly-opposed effects on nitration reaction--study on myeloperoxidase-deficient patient and myeloperoxidase-knockout mice.
Myeloperoxidase (MPO) catalyzes a nitration reaction to form nitrotyrosine in the presence of high nitrite, the metabolite of NO. Human leukocyte was shown to cause phenolic nitration using released MPO as a catalyst in the presence of nitrite. It opposes our previous finding that inhibition of MPO was essential for phenol nitration in human leukocyte study. To clarify the role of MPO, we utilized MPO-deficient human leukocytes and MPO-knockout mice. Even in the absence of exogenously added nitrite, high nitration product was observed in MPO-deficient leukocytes. In liver subjected to ischemia/reperfusion injury, a significantly higher amount of nitrotyrosine was produced in MPO-knockout mice than in normal mice. These results clearly demonstrate that MPO inhibits the accumulation of nitration products in vivo. Further experiments showed that MPO could degrade nitrotyrosine in the presence of glutathione. Thus, MPO-induced degradation of nitration products may cause the underestimation of the nitration product generated in vivo. We conclude that MPO may act predominantly to scavenge nitrotyrosine under physiological nitrite condition, and protect against injurious effect of nitrotyrosine.
Ichimori
Kohji
K
Department of Physiology, School of Medicine, Tokai University, Kanagawa, Ischera 259-1193, Japan. ichimori@is.icc.u-tokai.ac.jp
Fukuyama
Naoto
N
Nakazawa
Hiroe
H
Aratani
Yasuaki
Y
Koyama
Hideki
H
Takizawa
Shunya
S
Kameoka
Yosuke
Y
Ishida-Okawara
Akiko
A
Kohi
Fumikazu
F
Suzuki
Kazuo
K
D000328:Adult; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000378:metabolism; D015538:Nitrosation; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D009566:Nitrates; D009573:Nitrites; D026361:Reactive Nitrogen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D009195:Peroxidase; D009585:Nitrogen Dioxide