Brush border membrane proteins in experimental Fanconi's syndrome induced by 4-pentenoate and maleate.
Fanconi's syndrome was investigated using brush border membrane (BBM) vesicles isolated from dog kidney. Sodium-dependent uptake of glucose, phosphate, and amino acids and protein phosphorylation were studied in BBM isolated from normal and from 4-pentenoate- and maleate-treated animals. The time course of D-glucose and phosphate uptake, in BBM vesicles, remained unchanged, indicating that both treatments had no effect on carrier properties, and that permeabilities to these substrates and to sodium were not modified. Furthermore, sodium-dependent transport of alanine, phenylalanine, proline, glycine, and glutamate into vesicles remained unaltered by either treatment. 4-Pentenoate treatment caused modifications of the phosphorylation pattern of BBM proteins: the phosphorylation of two proteins (61 and 74 kDa) was increased and that of two others (48 and 53 kDa) was decreased. Maleate treatment caused an increase in the phosphorylation for the same 61-kDa protein, which was also affected by 4-pentenoate treatment, suggesting that phosphorylation of this protein could be related to a mechanism involved in both 4-pentenoate- and maleate-induced Fanconi's syndrome. These changes were also observed in the presence of sodium fluoride and L-bromotetramisole, indicating that the modification of phosphorylation was not due to a difference in phosphatase activities. These results suggest that Fanconi's syndrome induced by 4-pentenoate or maleate is not caused by an inhibition of BBM Na(+)-dependent transport systems. Our results also suggest that protein phosphorylation may play an important role in the molecular defect involved in Fanconi's syndrome.
Pouliot
J F
JF
Départements de chimie et biochimie, Université du Québec, Montréal, Canada.
Gougoux
A
A
Béliveau
R
R
D000818:Animals; D001692:Biological Transport; D004195:Disease Models, Animal; D004285:Dogs; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated; D005947:Glucose / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008298:Maleates; D008565:Membrane Proteins / Q000378:metabolism*; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013268:Stimulation, Chemical
D005229:Fatty Acids, Monounsaturated; D008298:Maleates; D008565:Membrane Proteins; C030272:maleic acid; C009785:4-pentenoic acid; D005947:Glucose