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doi:10.1016/j.freeradbiomed.2005.01.005 
Copyright © 2005 Elsevier Inc. All rights reserved.
Original Contribution
Arginase-1 overexpression induces cationic amino acid transporter-1 in psoriasis
Oliver Schnorra, 
, 
, Maximilian Schuiera, Guido Kagemanna, Ronald Wolfc, Markus Walzc, Thomas Ruzickac, Ertan Mayatepekd, Maurice Laryead, Christoph V. Suschekb, Victoria Kolb-Bachofenb and Helmut Siesa
Received 11 November 2004;
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Abstract
Regulated uptake of extracellular l-arginine by cationic amino acid transporters (CATs) is required for inducible nitric oxide synthase and arginase activity. Both enzymes were recently recognized as important in the pathophysiology of psoriasis because of their contribution to epidermal hyperproliferation. We here characterize the expression pattern of CATs in psoriatic skin compared to healthy skin. CAT-1 mRNA expression was strongly upregulated in lesional and nonlesional areas of psoriatic skin compared to healthy skin, whereas expression of CAT-2A and the inducible isoform CAT-2B was unaltered in psoriatic skin. Furthermore, we tested the hypothesis that arginase-1 overexpression regulates CAT expression via intracellular l-arginine concentration. In in vitro experiments with arginase-1 overexpressing HaCaT cells, CAT-1 mRNA expression was increased. Likewise, this occurs in l-arginine-starved HaCaT cells. Both CAT-2 isoforms were not affected. Arginase-1 overexpression limits the synthesis of NO at physiological, but not supraphysiological, l-arginine levels. Plasma l-arginine concentration was diminished in psoriasis patients and the arginase product l-ornithine was significantly increased compared to healthy controls. In summary, arginase-1 overexpression leads to upregulated CAT-1 expression in psoriatic skin, which is due to lowered intracellular l-arginine levels and limits NO synthesis at physiological l-arginine concentrations.
Keywords: Psoriasis; Cationic amino acid transporter; l-Arginine; Nitric oxide; Arginase; Free radicals
Abbreviations: CAT, cationic amino acid transporter; cNOS, constitutive nitric oxide synthase; iNOS, inducible nitric oxide synthase; RT-PCR, reverse-transcriptase–polymerase chain reaction
Article Outline
- Introduction
- Materials and methods
- Materials
- Patients and skin biopsies
- RNA Isolation and reverse-transcriptase–PCR
- Quantitative gene expression analysis
- Sequencing of PCR fragments
- Nitric oxide synthase activity
- Arginase activity
- Arginase-1 transfection
- Sequencing of Arginase-1 DNA fragments
- Amino acid analyses
- Statistical analyses
- Results
- Arginase-1 overexpression limits iNOS activity
- Intracellular l-arginine depletion leads to upregulated CAT-1 expression
- CAT-1 is upregulated in psoriatic skin
- Plasma l-arginine is diminished in psoriasis patients
- Discussion
- Arginase-1 overexpression limits NO synthesis and induces CAT-1 expression
- Upregulated CAT-1 expression in psoriasis
- Acknowledgements
- References
