Differential regulation of L-arginine transporters (cationic amino acid transporter-1 and -2) by peroxynitrite in rat mesangial cells.
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.
Schwartz
Idit Feenberg
IF
Department of Nephrology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv, Israel. nmdri@netvision.net.il
Chernichovsky
Tamara
T
Hagin
David
D
Ingbir
Meirav
M
Reshef
Ran
R
Chernin
Gil
G
Levo
Yoram
Y
Schwartz
Doron
D
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics / Q000502:physiology*; D027202:Cationic Amino Acid Transporter 2 / Q000235:genetics / Q000502:physiology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D012333:RNA, Messenger; D030421:Peroxynitrous Acid; D001120:Arginine