The stimulation of arginine transport by TNFα in human endothelial cells depends on NF-κB activation

6533b86dfe1ef96bd12cab99

RESEARCH PRODUCT

The stimulation of arginine transport by TNFα in human endothelial cells depends on NF-κB activation

Roberto Sala Francesco Alamanni Ovidio Bussolati Gian C. Gazzola Rossana Visigalli Alessandro Parolari Valeria Dall'asta Bianca Maria Rotoli Amelia Barilli

subject

MAPK/ERK pathway Lipopolysaccharides medicine.medical_specialty Umbilical Veins Time Factors CAT transporter Arginine Transcription Genetic p38 mitogen-activated protein kinases medicine.medical_treatment Biophysics Pharmacology Biology Arginine Polymerase Chain Reaction p38 Mitogen-Activated Protein Kinases Biochemistry Interferon-gamma Internal medicine Cations medicine TNFα Humans Interferon gamma RNA Messenger Cationic Amino Acid Transporter 2 Cells Cultured Protein Kinase C Arginine transport Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha NF-kappa B Biological Transport Cell Biology Cytokine Endocrinology SLC7 gene Amino Acid Transport Systems Basic Cytokines Tumor necrosis factor alpha Endothelium Vascular Signal transduction Mitogen-Activated Protein Kinases Peptides medicine.drug Interleukin-1 Signal Transduction NFκB

description

In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-alpha (TNFalpha) and bacterial lipopolysaccharide (LPS), but neither interferon gamma (IFNgamma) nor interleukin 1beta (IL-1beta), stimulate arginine transport. The effects of TNFalpha and LPS are due solely to the enhancement of system y+ activity, whereas system y+L is substantially unaffected. TNFalpha causes an increased expression of SLC7A2/CAT-2B gene while SLC7A1/CAT-1 expression is not altered by the cytokine. The suppression of PKC-dependent transduction pathways, obtained with the inhibitor chelerytrhine, the inhibitor peptide of PKCzeta isoform, or chronic exposure to phorbol esters, does not prevent TNFalpha effect on arginine transport. Likewise, ERK, JNK, and p38 MAP kinases are not involved in the cytokine effect, since arginine transport stimulation is unaffected by their specific inhibitors. On the contrary, inhibitors of NF-kappaB pathway hinder the increase in CAT2B mRNA and the stimulation of arginine uptake. These results indicate that in human endothelial cells the activation of NF-kappaB pathway mediates the TNFalpha effects on arginine transport.

year	journal	country	edition	language
2004-07-01	Biochimica et Biophysica Acta (BBA) - Biomembranes

10.1016/j.bbamem.2004.04.001 http://dx.doi.org/10.1016/j.bbamem.2004.04.001