Aortic arginine transport is attenuated, through post-translational modulation of CAT-1 by PKCalpha, in old male rats.
Experimental models using rats suggest that decreased endothelial nitric oxide synthase (eNOS) activity in old males promotes renal atherosclerosis, whereas females are protected. We aimed to explore whether aging alters aortic arginine uptake by CAT-1, the selective arginine supplier to eNOS in rats. Arginine uptake by freshly harvested aortic rings from young males (9 weeks) was significantly higher than in young females. Old males (18 months) exhibited a significant decrease in arginine transport compared to young males, whereas no differences were observed between old and young females. Cationic amino acid transporter-1 (CAT-1) abundance remained unchanged in all experimental groups. The abundance of protein kinase C alpha (PKCalpha), a CAT-1 inhibitor, was significantly augmented in old versus young males while no differences were detected between old and young females. Phosphorylated PKCalpha was significantly increased in old rats of both sexes. alphaTocopherol, a PKC inhibitor, produced a significant increase in arginine transport in old males only. In conclusion, aortic arginine transport by CAT-1 is attenuated in old male rats through upregulation of PKCalpha. In old females, aortic arginine transport is protected from the effects of PKCalpha by an unknown mechanism.
Schwartz
Idit F
IF
Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
Chernichovski
Tamara
T
Schwartz
Doron
D
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology*; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000494:pharmacology
D027201:Cationic Amino Acid Transporter 1; D047428:Protein Kinase Inhibitors; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051571:Protein Kinase C-alpha; D024502:alpha-Tocopherol