Differential regulation of l-arginine transporters (cationic amino acid transporter-1 and -2) by peroxynitrite in rat mesangial cells

• Published in: Nephrology, dialysis, transplantation Vol. 21; no. 12; pp. 3409 - 3414
• Main Authors: Schwartz, Idit Feenberg, Chernichovsky, Tamara, Hagin, David, Ingbir, Meirav, Reshef, Ran, Chernin, Gil, Levo, Yoram, Schwartz, Doron
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-12-2006; Oxford Publishing Limited (England)
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Arginine - metabolism; Biological and medical sciences; Cationic Amino Acid Transporter 1 - genetics; Cationic Amino Acid Transporter 1 - physiology; Cationic Amino Acid Transporter 2 - genetics; Cationic Amino Acid Transporter 2 - physiology; Emergency and intensive care: renal failure. Dialysis management; Fundamental and applied biological sciences. Psychology; Glomerulonephritis; Intensive care medicine; l-arginine transport; Medical sciences; Mesangial Cells - drug effects; Mesangial Cells - metabolism; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; nitric oxide; Peroxynitrous Acid - physiology; Rats; Rats, Wistar; reactive oxygen species; RNA, Messenger - biosynthesis; Vertebrates: urinary system; Kidney disease; Oxygen; Urinary system disease; Rat; Mesangial cell; Hemodialysis; Rodentia; L-arginine transport; Extrarenal dialysis; Vertebrata; Mammalia; Arginine; Aminoacid; Animal; Nitric oxide; Renal failure; reactive oxygen species; Transport
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfl522

Background. It has become evident that increased nitric oxide (NO) generation may be associated with production of reactive oxygen species, such as peroxynitrite (ONOO−). Peroxynitrite has been postulated to be responsible for several of the cytotoxic effects previously ascribed to NO. Since cellular arginine uptake has been shown to modulate nitric oxide synthase activity, we were intrigued to study the effect of ONOO− on arginine traffic in renal mesangial cells. Methods. Arginine uptake, CAT-1 and CAT-2 mRNA expression by northern blotting analysis, and CAT-1 protein content using western blotting were determined in mesangial cells pre-treated with peroxynitrite (0.1 and 0.5 mM) for 2 h. Results. Peroxynitrite induced a significant increase in arginine uptake and CAT-2 mRNA expression compared with untreated cells. In contrast, CAT-1 mRNA expression and protein abundance were diminished. Conclusions. In rat mesangial cells, peroxynitrite augments arginine uptake via augmentation of CAT-2 while decreasing CAT-1 expression.