Coinduction of nitric oxide synthase and arginine metabolic enzymes in endotoxin-induced uveitis rats

Exp Eye Res. 2002 Dec;75(6):659-67. doi: 10.1006/exer.2002.2062.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / biosynthesis
  • Arginase / genetics
  • Arginine / metabolism*
  • Argininosuccinate Synthase / genetics
  • Disease Models, Animal
  • Enzyme Induction
  • Lipopolysaccharides
  • Male
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Uveitis / etiology
  • Uveitis / metabolism*
  • Uveitis / pathology

Substances

  • Lipopolysaccharides
  • RNA, Messenger
  • Nitric Oxide
  • Arginine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Arginase
  • Argininosuccinate Synthase