STRESS DIFFERENTIALLY INDUCES CATIONIC AMINO-ACID TRANSPORTER GENE-EXPRESSION

The amino acid L-arginine plays a central role in several adaptive met abolic pathways and we postulate that regulated L-arginine transport c ontributes to important physiological responses. The majority of L-arg inine flux is mediated by transport system y(+) that is encoded by at least three genes, Cat1, Cat2 and Cat3. Cat2 encodes two distinct prot ein isoforms (CAT2/CAT2a) that differ by 10-fold in their apparent sub strate affinity. Cat2 transcription is controlled by four widely space d promoters, The expression of CAT2/2a transcripts was tested in skele tal muscle and macrophages following specific stresses or activators. Unexpectedly, CAT2a transcripts accumulated in skeletal muscle in resp onse to surgical trauma (hepatectomy and splenectomy) as well as food deprivation, although neither high affinity CAT2 nor CAT1 were detecta bly altered. Activated macrophages decreased CAT1 levels, but accumula ted CAT2 and iNOS mRNA and protein with parallel kinetics suggesting t hat CAT2 mediated r-arginine transport might regulate the r-arginine:n itric oxide pathway. In macrophages, liver and skeletal muscle, the mo st distal CAT2 promoter was predominant. No change in promoter usage w as apparent under any stress conditions tested nor was alternate splic ing of the CAT2 transcript dictated by promoter usage. The differentia l regulation of the Cat genes indicates their encoded transporter prot eins meet different requirements for cationic amino acids in the intac t animal. (C) 1998 Elsevier Science B.V. All rights reserved.