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-[3H]Arginine transport capacity in human PTEC is increased after exposure for 24 h to human albumin, mediated by the broad-scope high-affinity system b0,+ and, to a lesser extent, system y+L (but not system y+) transport. Increased transport is associated with increased b0,+-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 b0,+ transport system. This may make L-arginine available as a substrate for the downstream synthesis of polyamines, but is not critical for cell proliferation.
Increased L-arginine transport via system b0,+ in human proximal tubular cells exposed to albumin
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Neil Ashman, Tatiana M. Brunini, Giovanni E. Mann, A. Claudio Mendes Ribeiro, Muhammad M. Yaqoob; Increased L-arginine transport via system b0,+ in human proximal tubular cells exposed to albumin. Clin Sci (Lond) 1 December 2006; 111 (6): 389–399. doi: https://doi.org/10.1042/CS20060158
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