Na+,K+-ATPase Expression in Maleic-Acid-Induced Fanconi Syndrome in Rats

Abstract

1. Na+,K+-ATPase activity and its α1 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 α1 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 nonspecific and involve a great variety of proteins, but seems to be restricted to selected tissues because α1 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.