CATIONIC AMINO-ACID TRANSPORTER-2 MESSENGER-RNA INDUCTION BY TUMOR-NECROSIS-FACTOR-ALPHA IN VASCULAR ENDOTHELIAL-CELLS

Nitric oxide (NO) synthesis may be coupled to the activity of the cell ular L-arginine transporter, namely the cationic amino acid transporte r. The present study examined tumor necrosis factor (TNF)-alpha-induce d alterations in the gene expression of the cationic amino acid transp orter (CAT) and NO production in human umbilical vein endothelial cell s. In quiescent endothelial cells, CAT-1 mRNA expression, determined b y reverse transcription-polymerase chain reaction, was dominant to tha t of CAT-2. TNF-alpha (10 ng/ml for 1-24 h) induced a time-dependent i ncrease in CAT-2 but not CAT-1 expression. Moreover, TNF-alpha (1-30 n g/ml) treatment for 6 h induced a concentration-dependent increase in CAT-2 mRNA expression. The upregulation of CAT-2 expression by TNF-alp ha was associated with enhanced nitrite accumulation in the culture me dium (70% increase compared with vehicle-treated cells at 24 h). Thus, induction of the cationic amino acid transporter may constitute one m echanism for the TNF-alpha-induced NO production in human umbilical ve in endothelial cells. (C) 1997 Elsevier Science B.V.