title: Shiga toxin-1 affects nitric oxide production by human glomerular endothelial and mesangial cells.
abstract: Acute renal failure hallmarks the pathogenesis of the epidemic form of hemolytic uremic syndrome (D+HUS), which is caused by E. coli strains that produce Shiga-like toxin (Stx). In this study, we investigated the influence of Stx-1 on nitric oxide (NO) production by human glomerular microvascular endothelial cells (GMVEC) and human mesangial cells. NO synthesis by human mesangial cells is in the micromolar range and that of GMVEC in the picomolar range. Stx-1 reduced NO production in non-stimulated GMVEC (5 nmol/l Stx-1 required) without inhibition of protein synthesis. In non-stimulated and TNFalpha-pretreated mesangial cells, NO production was reduced with a maximal reduction at 10 fmol/l shiga toxin. The cellular iNOS antigen content in mesangial cells was reduced in a concentration-dependent way (10 fmol/l-100 pmol/l), while partial inhibition of protein synthesis required 10 nmol/l Stx-1 in these cells. Our in vitro data suggest that Stx may reduce NO synthesis during the course of HUS development, contributing to the aggravation of the thrombotic microangiopathy and renal failure as observed in HUS.
authors.affiliation: Department of Pediatrics, University Hospital Nijmegen, Nijmegen, The Netherlands.
authors.forename: D Maroeska
authors.initials: DM
authors.lastname: Te Loo
authors.forename: Leo
authors.initials: L
authors.lastname: Monnens
authors.forename: Thea
authors.initials: T
authors.lastname: van der Velden
authors.forename: Mohammed
authors.initials: M
authors.lastname: Karmali
authors.forename: Lambertus
authors.initials: L
authors.lastname: van den Heuvel
authors.forename: Victor
authors.initials: V
authors.lastname: van Hinsbergh
mesh_terms: D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000201:enzymology; D050527:Mesangial Cells / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D022622:Shiga Toxin 1 / Q000494:pharmacology*
chemical_list: D022622:Shiga Toxin 1; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III