Late-onset downregulation of NaPi-2 in experimental Fanconi syndrome.
The pathogenesis of renal phosphate (Pi) leak in Fanconi syndrome is unknown. Disorders of apical membrane transporters, leaky apical membrane, depleted cellular Pi and ATP, and impaired sodium (Na) pumps have been proposed as underlying defects. The present study examined the role of type II Na-Pi cotransport system (NaPi-2) in experimental Fanconi syndrome in rats. Following a single injection of maleic acid (MA), 75 mg/kg body weight i.p., rats were sacrificed after 90 min, 4 h, and 24 h. Renal cortical expression of NaPi-2 mRNA was determined by Northern blotting, and brush border membrane (BBM) NaPi-2 protein by Western blotting. Increased urinary excretion of phosphate was demonstrated as soon as 90 min after MA injection, and was sustained at 4 and 24 h, NaPi-2 mRNA expression and NaPi-2 protein were not decreased after 90 min. NaPi-2 mRNA decreased after 4 h, while NaPi-2 protein decreased only at 24 h. Hence, the immediate phosphaturia in experimental Fanconi syndrome may be independent of NaPi-2 downregulation, possibly resulting from energy depletion or membrane dysfunction. The decrease in NaPi-2 mRNA expression and the subsequent NaPi-2 protein decrease may account for the second-phase phosphaturia.
Haviv
Y S
YS
Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, POB 12000, Jerusalem, Israel 91120.
Wald
H
H
Levi
M
M
Dranitzki-Elhalel
M
M
Popovtzer
M M
MM
D000818:Animals; D001693:Biological Transport, Active; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis*; D015536:Down-Regulation / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000652:urine*; D015151:Immunoblotting; D007672:Kidney Cortex / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008298:Maleates; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000652:urine*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
D002352:Carrier Proteins; D008298:Maleates; D010710:Phosphates; D012333:RNA, Messenger; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; C030272:maleic acid