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NDT Advance Access originally published online on September 23, 2006
Nephrology Dialysis Transplantation 2006 21(12):3409-3414; doi:10.1093/ndt/gfl522
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Idit Feenberg Schwartz, Tamara Chernichovsky, David Hagin, Meirav Ingbir, Ran Reshef, Gil Chernin, Yoram Levo and Doron Schwartz

Nephrology Department, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel

Correspondence and offprint requests to: Idit F. Schwartz, Department of Nephrology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, Israel. Email: nmdri{at}netvision.net.il

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.

Keywords: L-arginine transport; nitric oxide; reactive oxygen species


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