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Stress differentially induces cationic amino acid transporter gene expression
D K Kakuda1, K D Finley, M Maruyama
1UCSD Cancer Center, Cancer Genetics Program and Department of Medicine, University of California, San Diego, CA, USA.
Biochimica Et Biophysica Acta
|November 7, 1998
Summary
Regulated L-arginine transport is crucial for physiological responses. The Cat2 gene
Area of Science:
- Cellular biology
- Molecular biology
- Physiology
Background:
- L-arginine is vital for adaptive metabolic pathways.
- L-arginine transport is primarily mediated by the y+ system, encoded by Cat1, Cat2, and Cat3 genes.
- The Cat2 gene produces two isoforms, CAT2 and CAT2a, with differing substrate affinities.
Purpose of the Study:
- To investigate the regulation of Cat gene expression under various physiological stresses.
- To determine the role of L-arginine transport in adaptive responses.
- To explore the relationship between L-arginine transport and the nitric oxide pathway.
Main Methods:
- Analysis of Cat1, Cat2, and Cat3 gene expression in skeletal muscle and macrophages.
- Assessment of CAT2/CAT2a transcript accumulation following surgical trauma, food deprivation, and macrophage activation.
- Investigation of Cat2 promoter usage and its regulation under stress conditions.
Main Results:
- CAT2a transcripts unexpectedly accumulated in skeletal muscle after surgical trauma and food deprivation.
- Activated macrophages showed decreased CAT1 levels but increased CAT2 and iNOS mRNA and protein.
- The distal Cat2 promoter was predominant across tissues, with no changes observed under stress.
Conclusions:
- Differential regulation of Cat genes suggests distinct roles for their encoded transporters in amino acid transport.
- Cat2-mediated L-arginine transport may play a significant role in regulating the L-arginine:nitric oxide pathway.
- Specific stresses induce differential expression of L-arginine transporters, highlighting their adaptive importance.