Coinduction of nitric oxide synthase and arginine metabolic enzymes in endotoxin-induced uveitis rats.
The regulation of expression of the arginine-recycling enzymes and arginase isoforms in association with inducible nitric oxide synthase (iNOS) in the eye of endotoxin-induced uveitis (EIU) rats is investigated. An animal model of EIU was created in Wistar rats by intravitreal injection of lipopolysaccharide (LPS). mRNAs for argininosuccinate synthase (AS) and arginase I as well as for iNOS, measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), were induced in the eye of EIU rats. iNOS mRNA increased markedly 3 hr after injection, reached a maximum at 6-12 hr, and then decreased at 24 hr. AS mRNA remained little change at 3 hr and increased maximally at 6 hr (by about 3.3-fold), whereas arginase I mRNA increased later and reached a maximum at 12 hr (by about 4.2-fold). iNOS, AS, and arginase I proteins were also induced. AL and arginase II mRNAs remained little changed. In immunohistochemical analysis, iNOS, AS and arginase I were almost colocalized in infiltrated inflammatory cells in the vitreous, iris, ciliary body and inner layers of the retina. In conclusion, AS and arginase I are coinduced with iNOS in infiltrated inflammatory cells in the eyes of EIU rats, and may regulate NO production by changing intracellular concentration of arginine.
Koga
Takahisa
T
Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto, Japan.
Koshiyama
Yasuo
Y
Gotoh
Tomomi
T
Yonemura
Naoko
N
Hirata
Akira
A
Tanihara
Hidenobu
H
Negi
Akira
A
Mori
Masataka
M
D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics; D001120:Arginine / Q000378:metabolism*; D001124:Argininosuccinate Synthase / Q000235:genetics; D004195:Disease Models, Animal; D004790:Enzyme Induction; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014605:Uveitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001119:Arginase; D001124:Argininosuccinate Synthase