Inhibition of water absorption in human proximal tubular epithelial cells in response to Shiga toxin-2

SILBERSTEIN CLAUDIA; PISTONE CREYDT VIRGINIA; GERHARDT ELIZABETH; NÚÑEZ PABLO; IBARRA CRISTINA

PEDIATRIC NEPHROLOGY

Springer International

Año: 2008 vol. 23 p. 1981 - 1990

0931-041X

Postdiarrhea hemolytic uremic syndrome (HUS)is the most common cause of acute renal failure in childrenin Argentina. It is well established that Shiga toxin type 2(Stx2) causes direct damage to glomerular endothelial cellsand tubular epithelial cells, leading to a reduction in thewater handling capacity of the kidney. In this study, wedemonstrate that Stx2 and its B subunit (Stx2B) were ableto inhibit water absorption across human renal tubularepithelial cell (HRTEC) monolayers without altering theshort circuit current and the 3H-mannitol permeability.Quantitative evaluation of 14C-inulin transport acrossHRTEC monolayers showed a similar transport rate bothbefore and after HRTEC treatment with Stx2 that confirmedthe integrity of the paracellular pathway. Furthermore, Stx2produced significant protein synthesis inhibition of HRTECat concentrations as low as 0.001 ng/ml and 1 h ofincubation, whereas Stx2B did not modify it at concentrationsas high as 10,000 ng/ml and 6 h of incubation. Ourfindings suggest that whereas the action of Stx2 appears tobe caused mainly by the inhibition of protein synthesismediated by the A subunit, the binding of Stx2B subunit tothe Gb3 receptor may affect the membrane mechanismsrelated to water absorption. We speculate that inhibition ofwater absorption may occur in proximal tubular cells invivo in response to Stx2 and may contribute to the earlyevent of HUS pathogenesis.