The stimulation of arginine transport by TNFalpha in human endothelial cells depends on NF-kappaB activation.
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.
Visigalli
Rossana
R
Dipartimento di Medicina Sperimentale, Sezione di Patologia Generale e Clinica, Università degli Studi di Parma, Via Volturno, 39 Parma 43100, Italy.
Bussolati
Ovidio
O
Sala
Roberto
R
Barilli
Amelia
A
Rotoli
Bianca Maria
BM
Parolari
Alessandro
A
Alamanni
Francesco
F
Gazzola
Gian C
GC
Dall'Asta
Valeria
V
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
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