title: The stimulation of arginine transport by TNFalpha in human endothelial cells depends on NF-kappaB activation.
abstract: 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.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Patologia Generale e Clinica, Università degli Studi di Parma, Via Volturno, 39 Parma 43100, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Visigalli
authors.forename: Ovidio
authors.initials: O
authors.lastname: Bussolati
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala
authors.forename: Amelia
authors.initials: A
authors.lastname: Barilli
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Rotoli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Parolari
authors.forename: Francesco
authors.initials: F
authors.lastname: Alamanni
authors.forename: Gian C
authors.initials: GC
authors.lastname: Gazzola
authors.forename: Valeria
authors.initials: V
authors.lastname: Dall'Asta
mesh_terms: D026923:Amino Acid Transport Systems, Basic; D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D027202:Cationic Amino Acid Transporter 2 / Q000378:metabolism / Q000502:physiology*; D002412:Cations; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases; D000099221:Protein Kinase C zeta
chemical_list: D026923:Amino Acid Transport Systems, Basic; D001120:Arginine; D027202:Cationic Amino Acid Transporter 2; D002412:Cations; D016207:Cytokines; D007371:Interferon-gamma; D007375:Interleukin-1; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D010455:Peptides; D011493:Protein Kinase C; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099221:Protein Kinase C zeta; C414177:SLC7A2 protein, human