Schnorr Oliver, Schuier Maximilian, Kagemann Guido, Wolf Ronald, Walz Markus, Ruzicka Thomas, Mayatepek Ertan, Laryea Maurice, Suschek Christoph V, Kolb-Bachofen Victoria, Sies Helmut
Institute for Biochemistry and Molecular Biology I, Building 22.03, Heinrich-Heine-University Duesseldorf, Universitaetsstr.1, D-40225 Duesseldorf, Germany.
Free Radic Biol Med. 2005 Apr 15;38(8):1073-9. doi: 10.1016/j.freeradbiomed.2005.01.005.
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.
阳离子氨基酸转运体（CATs）对细胞外L-精氨酸的调节性摄取是诱导型一氧化氮合酶和精氨酸酶活性所必需的。由于这两种酶对表皮过度增殖有作用，它们最近被认为在银屑病的病理生理学中很重要。我们在此描述银屑病皮肤与健康皮肤相比CATs的表达模式。与健康皮肤相比，银屑病皮肤的皮损区和非皮损区中CAT-1 mRNA表达强烈上调，而银屑病皮肤中CAT-2A和诱导型异构体CAT-2B的表达未改变。此外，我们测试了精氨酸酶-1过表达通过细胞内L-精氨酸浓度调节CAT表达的假设。在精氨酸酶-1过表达的HaCaT细胞的体外实验中，CAT-1 mRNA表达增加。同样，在L-精氨酸饥饿的HaCaT细胞中也会发生这种情况。两种CAT-2异构体均未受影响。在生理水平而非超生理水平的L-精氨酸浓度下，精氨酸酶-1过表达会限制NO的合成。银屑病患者的血浆L-精氨酸浓度降低，与健康对照相比，精氨酸酶产物L-鸟氨酸显著增加。总之，精氨酸酶-1过表达导致银屑病皮肤中CAT-1表达上调，这是由于细胞内L-精氨酸水平降低，并在生理L-精氨酸浓度下限制了NO的合成。
