title: Increased L-arginine transport via system b0,+ in human proximal tubular cells exposed to albumin.
abstract: Albumin has complex effects on PTECs (proximal tubular epithelial cells) and is able to stimulate growth or injury depending on its bound moieties. Albumin itself is a mitogen, inducing proliferation through a number of pathways. In PTEC exposed to purified albumin, polyamines are required for entry into the cell cycle and are critical for proliferation. Polyamines are synthesized from L-ornithine (itself derived by the action of arginase on L-arginine), and the transport and availability of L-arginine may thus be important for subsequent polyamine-dependent proliferation. In the present study we investigated radiolabelled cationic amino-acid transport in cultured PTEC exposed to 20 mg/ml ultrapure recombinant human albumin, describing the specific kinetic characteristics of transport and the expression of transporters. L-[(3)H]Arginine transport capacity in human PTEC is increased after exposure for 24 h to human albumin, mediated by the broad-scope high-affinity system b(0,+) and, to a lesser extent, system y(+)L (but not system y(+)) transport. Increased transport is associated with increased b(0,+)-associated transporter expression. Inhibition of phosphoinositide 3-kinase, a key regulator of albumin endocytosis and signalling, inhibited proliferation, but had no effect on the observed increase in transport. PTEC proliferated in response to albumin. L-Lysine, a competitive inhibitor of L-arginine transport, had no effect on albumin-induced proliferation; however, arginine deprivation effectively reversed the albumin-induced proliferation observed. In conclusion, in PTEC exposed to albumin, increased L-arginine transport is mediated by increased transcription and activity of the apical b(0,+) transport system. This may make L-arginine available as a substrate for the downstream synthesis of polyamines, but is not critical for cell proliferation.
authors.affiliation: Department of Experimental Medicine, Critical Care and Nephrology, William Harvey Research Institute, Queen Mary College, University of London, London, UK. neil.ashman@bartsandthelondon.nhs.uk
authors.forename: Neil
authors.initials: N
authors.lastname: Ashman
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Brunini
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Mendes Ribeiro
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Yaqoob
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D026923:Amino Acid Transport Systems, Basic / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000418:Albumins; D026923:Amino Acid Transport Systems, Basic; D012333:RNA, Messenger; D011994:Recombinant Proteins; D001120:Arginine; D019869:Phosphatidylinositol 3-Kinases