Endogenous and new synthetic antioxidants for peroxynitrite: selective inhibitory effect of 5-methoxytryptamine and lipoic acid on tyrosine nitration by peroxynitrite.
The inhibitory effects of endogenous and synthetic compounds on the nitration and oxidation of L-tyrosine by peroxynitrite were examined. Nitration and oxidation activities of L-tyrosine by peroxynitrite were estimated by monitoring the formation of 3-nitrotyrosine and dityrosine with a high-performance liquid chromatography-ultraviolet (HPLC-UV)-fluorescence detector system. Glutathione and synthetic compounds ((2S,3R,4S)-N-ethylmercapto-3,4-dihydroxy-2-hydroxymethylpyrrolidine, L-N-dithiocarboxyproline) inhibited both the nitration and the oxidation reactions of L-tyrosine effectively. On the other hand, 5-methoxytryptamine and lipoic acid inhibited only the nitration reaction of L-tyrosine, and instead increased the oxidation reaction. It was assumed that 5-methoxytryptamine and lipoic acid reacted only with the nitrating species of peroxynitrite. This is the first report of a selective inhibitor for the nitrating reaction of peroxynitrite.
Bioregulation Research Group, National Institute of Radiological Sciences, Chiba 263, Japan.
H
H
Nakagawa
E
E
Sumiki
N
N
Ikota
Y
Y
Matsushima
T
T
Ozawa
D008735:5-Methoxytryptamine / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D015259:Dopamine Agents / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism; D009566:Nitrates / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016877:Oxidants / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D015259:Dopamine Agents; C422417:N-dithiocarboxyproline; C422416:N-ethylmercapto-3-4-dihydroxy-2-hydroxymethylpyrrolidine; D009566:Nitrates; D016877:Oxidants; D011759:Pyrrolidines; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D008735:5-Methoxytryptamine; D014443:Tyrosine; D007980:Levodopa; D008063:Thioctic Acid; D011392:Proline; C007543:dityrosine