ELIGLUSTAT PREVENTS AGAINST THE CYTOTOXIC EFFECTS OF SHIGA TOXIN TYPE 2 IN HUMAN RENAL TUBULAR EPITHELIAL CELLS

FISCHER SIGEL KARINA ; AMARAL MARÍA M; BALESTRACCI ALEJANDRO; SILBERSTEIN CLAUDIA ; SANCHEZ DAIANA ; IBARRA CRISTINA

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

In Argentina, post-diarrhea HemolyticUremic Syndrome due to Shiga toxin-producing Escherichia Coliis a common cause of acute renal failure in children. Shiga toxintype 2 (Stx2) binds to the globotriaosylceramide (Gb3) receptoron the surface of renal cells. We have previously shown that thecompound C-9 (Genzyme), an inhibitor of glucosylceramidesynthase (GLI-1), decreased Gb3 expression and prevents thecytotoxic actions of Stx2 in renal cells. The aim of the presentwork was to study whether Eliglustat (EG, MedKoo Biosci, USA),a new potent inhibitor of GLI-1, prevents the cytotoxic effects ofStx2 on primary cultures of human renal tubular epithelial cells(HRTEC) and HK-2, a human renal proximal tubule cell line.HRTEC were developed from nephrectomies performed at theHospital de Niños Pedro de Elizalde. Cells were pre-incubatedwith or without EG (1-1000 nM, 6-24 h), followed by coincubation with EG and Stx2 (10 ng/ml, 24-72 h). Cell viabilityand proliferation were measured by neutral red andbromodeoxyuridine uptake, respectively. Apoptosis wasevaluated by acridine orange/ethidium bromide staining.Treatment with Stx2 significantly decreased cell viability andproliferation and increased cell apoptosis in HRTEC and HK-2compared to control cells (p