Prevention of renal damage caused by Shiga toxin type 2: Action of Miglustat on human endothelial and epithelial cells

GIRARD MAGALI; SACERDOTI FLAVIA; RIVERA FULTON; REPETTO HORACIO A; IBARRA CRISTINA; AMARAL MARÍA MARTA

TOXICON

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 105 p. 27 - 33

0041-0101

<!-- /* Font Definitions */@font-face{font-family:Calibri;panose-1:2 15 5 2 2 2 4 3 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-parent:"";margin-top:0cm;margin-right:0cm;margin-bottom:10.0pt;margin-left:0cm;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Times New Roman";mso-ascii-font-family:Calibri;mso-fareast-font-family:Calibri;mso-hansi-font-family:Calibri;mso-bidi-font-family:"Times New Roman";mso-ansi-language:ES-AR;}@page Section1{size:612.0pt 792.0pt;margin:72.0pt 90.0pt 72.0pt 90.0pt;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.Section1{page:Section1;}-->Typical hemolytic uremic syndrome (HUS) is responsible for acute and chronic renalfailure in children younger than 5 years old in Argentina. Renal damages have been associated with Shiga toxintype 1 and/or 2 (Stx1, Stx2) produced by Escherichiacoli O157:H7, although strains expressing Stx2 are highly prevalent inArgentina. Human glomerular endothelial cells (HGEC) and proximal tubuleepithelial cells are very Stx-sensitive since they express high levels of Stxreceptor (Gb3). Nowadays, there is no available therapy to protect patientsfrom acute toxin-mediated cellular injury. New strategies have been developedbased on the Gb3 biosynthesis inhibition through blocking the enzymeglucosylceramide (GL1) synthase. Weassayed the action of a GL1 inhibitor (Miglustat: MG), on the preventionof the renal damage induced by Stx2.HGECprimary cultures and HK-2 cell line were pre-treated with MG and then incubatedwith Stx2. HK-2 and HGEC express Gb3 and MG was able to decrease the levels ofthis receptor. As a consequence, both types of cells were protected from Stx2 cytotoxicityand morphology damage. MG was able to avoid Stx2 effects in human renal cells and could be a feasible strategy to protect kidney tissuesfrom the cytotoxic effects of Stx2 in vivo.