Na+,K(+)-ATPase expression in maleic-acid-induced Fanconi syndrome in rats.
Na+,K(+)-ATPase activity and its alpha 1 subunit protein and mRNA in kidney cortex were monitored in rats developing Fanconi syndrome after the administration of maleate. Na+,K(+)-ATPase activity was significantly lower than in saline-injected controls, although this was partially mediated by a general, non-specific decrease in the cortex protein content. 2. The low activity of the sodium pump correlated with low abundance of alpha 1 subunit mRNA and protein levels. Hsp60 protein levels were also decreased in kidney cortex from maleate-treated rats. 3. Kidney cortex brush-border membrane vesicles from maleate-treated rats showed a marked decrease in Na(+)-dependent alanine and glucose transport, which was not dependent on the Na(+)-transmembrane gradient itself, a finding which is consistent with a more stable effect at the plasma membrane level. 4. The effect of maleate may be partially non-specific and involve a great variety of proteins, but seems to be restricted to selected tissues because alpha 1 subunit Na+,K(+)-ATPase and hsp60 protein amounts were not significantly modified in livers from rats developing Fanconi syndrome. 5. These results show that maleate administration induces a low activity of selected concentrative transport systems and a decrease in Na+,K(+)-ATPase activity and expression. The combination of both effects may explain the increased excretion of most organic solutes present in rats developing Fanconi syndrome.
Castaño
E
E
Department de Bioquímica i Biologia Molecular, Universitat de Barcelona, Spain.
Marzabal
P
P
Casado
F J
FJ
Felipe
A
A
Pastor-Anglada
M
M
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008298:Maleates; D008871:Microvilli / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D008298:Maleates; D012333:RNA, Messenger; C030272:maleic acid; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D000409:Alanine