Selective induction of a cationic amino acid transporter by tumor necrosis factor-alpha in vascular endothelium

Treatment of bovine aortic endothelial cells with tumor necrosis factor-alpha (TNF-alpha) resulted in a concentration-dependent increase in L-arginine transport. The stimulatory effect of TNF-alpha was time-dependent, requiring at least 6 hr of exposure. Both actinomycin D and cycloheximide inhibited the TNF-alpha mediated increase in L-arginine transport, indicating that de novo RNA and protein synthesis were required. Ribonuclease protection analysis revealed the presence of cationic amino acid transporter (CAT)-1 and CAT-2 mRNA. Treatment of bovine aortic endothelial cells with TNF-alpha selectively increased the levels of CAT-2 mRNA, whereas message for CAT-1 remained unchanged. These results demonstrate that TNF-alpha stimulates L-arginine transport in endothelial cells by selectively inducing the expression of CAT-2 mRNA. The capacity of TNF-alpha to stimulate the expression of CAT-2 protein may provide an important mechanism by which increases in substrate are provided to endothelial cells during periods of elevated L-arginine metabolism.