CAT2 arginine transporter deficiency significantly reduces iNOS-mediated NO production in astrocytes

被引：42

作者：

Manner, CK ^{[1
]}

Nicholson, B ^{[1
]}

MacLeod, CL ^{[1
]}

机构：

[1] Univ Calif San Diego, Ctr Canc, Biomed Sci Grad Progam, La Jolla, CA 92093 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2003年 / 85卷 / 02期

关键词：

arginine transport; astrocyte; cationic amino acid transporter 2; inducible nitric oxide synthase;

D O I：

10.1046/j.1471-4159.2003.01695.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have previously demonstrated that genetic ablation of cationic amino acid transporter 2 (Cat2 ) significantly inhibits nitric oxide (NO) production by inducible nitric oxide synthase (iNOS) in activated macrophages. Here we report that iNOS activity is impaired by 84% in activated Cat2-deficient astrocytes. Cat2 ablation appears to reduce astrocyte NO synthesis by decreasing the uptake of the sole precursor, arginine, as well as by reducing the expression of iNOS following activation. Excessive or dysregulated NO production by activated astrocytes and other CNS cell types has been implicated in the pathogenesis of neurological disorders. Our results support the idea that manipulation of CAT2 transporter function might be useful for the therapeutic modulation of iNOS activity.

引用

页码：476 / 482

页数：7

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