Effect of serum proteins on sodium-linked transport processes in cultured kidney cells.
The mechanism for increased Na+ retention in the nephrotic syndrome is unknown. To determine if Na+ transport systems in the proximal tubule might be affected by filtered proteins, mouse cortical tubule cells grown in defined medium were exposed to concentrations of bovine serum albumin (BSA) ranging from 0.01 to 0.5%. Activity of the Na(+)-glucose cotransporter, measured as Na(+)-dependent uptake of alpha-methylglucoside, increased progressively to a maximum of 2.3-fold above baseline (P < 0.001; N = 10). The increase in transporter activity was due to an increased Vmax, and the magnitude of the increase was inversely related to the basal cotransporter activity of the cultures. Increased cotransporter activity was detectable 6 h after exposure, was sustained for 24 h after cells were removed from an albumin-free medium, and was prevented by cycloheximide. Heat-treated BSA, fatty-acid and globulin-free BSA, and gamma-globulins were as effective at increasing Na(+)-glucose cotransporter activity as untreated Fraction V BSA. Dextran, dextran-sulfate, and amino acid supplements were ineffective. Neither protease inhibitors nor chloroquine added to an albumin-containing medium prevented increased alpha-methylglucoside uptake. Albumin did not change the rate of fluid-phase endocytosis in the cultured cells. Na(+)-amino acid cotransport and Na(+)-H+ exchange were either decreased or unchanged after BSA exposure. Exposing apical surfaces of cells grown on permeable membranes to BSA led to a greater increase in activity of the Na(+)-glucose cotransporter relative to controls than did exposing the basolateral surface (145 versus 89%; P < 0.05; N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Blumenthal
S S
SS
Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Lewand
D L
DL
Tipnis
P A
PA
Kleinman
J G
JG
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D003470:Culture Media; D005947:Glucose / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D000596:Amino Acids; D001798:Blood Proteins; D003470:Culture Media; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D017923:Sodium-Hydrogen Exchangers; D012710:Serum Albumin, Bovine; C027020:methylglucoside; D012964:Sodium; D005947:Glucose