Purchase this article with an account.
Chang-Hao Yang, Yi-An Lee, Chung-May Yang, Muh-Shy Chen; Expression of Inducible Nitric Oxide Synthase and Cationic Amino Acid Transporter (CAT) In Endotoxin-Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1244.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Nitric oxide (NO) plays a significant role in the pathogenesis of ocular inflammation. The synthesis of NO depends on cell membrane protein cationic amino acid transporter (CAT) to transfer arginine into the cell and inducible nitric oxide synthase (iNOS) to convert arginine into NO. The purpose of this study is to examine the expression of CAT and iNOS in endotoxin-induced uveitis (EIU).
EIU was induced by a footpad injection of 200 μg LPS in Lewis rats. Proteasome inhibitor bortezomib (valcade) was injected intraperitoneally 30 minutes before the LPS administration. The rats were sacrificed 24 hours later and the eyes were enucleated. The expression of iNOS and CAT mRNA and protein in the iris and ciliary body was determined by RT-PCT and Western blotting. The production of NO in aqueous was measured by ELISA. Immunochemical staining of the iris and ciliary body was performed to evaluate the inhibitory effect of valcade. . The interaction of NF-ΚB activation, CAT, and iNOS induction was assessed by electrophoretic mobility shift assay (EMSA).
Proteasome inhibitor valcade abrogated the inflammation of EIU as demonstrated by immunochemical stain and the decreased NO production in aqueous. The expression of iNOS and CAT mRNA and protein in EIU mouse eyes were suppressed by valcade. EMSA revealed that NF-ΚB activation was responsible for iNOS and CAT induction.
NF-ΚB is an essential transcription factor not only for the induction of iNOS, but also for the up-regulation of CAT. The simultaneous up-regulation of CAT and iNOS may play an important role in the pathogenesis of EIU.
This PDF is available to Subscribers Only