D-Glucose increases the expression and activity of hCAT-1 and Spl binding to SLC7A1 promoter in human umbilical vein endothelium
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Date
2008
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Abstract
L-Arginine is mainly transported by the human cationic amino acid transporter 1 (hCAT-1, protein codified by the gene SLC7A1) in human umbilical vein endothelial cells (HUVEC). hCAT-1 mediated L-arginine transport and nitric oxide (NO) synthesis are increased by 25 mM D-glucose in this cell type. Since Sp1 is a transcription factor activated by NO, we studied whether high D-glucose effect on transport was due to altered expression of hCAT-1 and abundance and activity of the transcription factor Sp1 in primary cultures of HUVEC. D-Glucose (25 mM, 24 hours) increased (~3.2 fold) the maximal velocity (Vmax), without altering the apparent Km, of L-arginine transport compared with cells in 5 mM D-glucose. High D-glucose also increased the hCAT-1 mRNA number of copies (~5-fold) and protein abundance (~2-fold), and Sp1 nuclear abundance and binding to SLC7A1 promoter region (−177 to −103 bp from ATG). Thus, the stimulatory effect of D-glucose on L-arginine transport could result from increased expression of hCAT-1 due to increased activity of Sp1 on the promoter of SLC7A1 in HUVEC.