Inhibition of Shiga Toxin Cytotoxicity in Human Renal Cortical Epithelial Cells by Nitrobenzylthioinosine

Abstract

Nitrobenzylthioinosine (NBTI), a nucleoside-transport inhibitor, has been found to possess the ability to prevent the cytotoxic action of Shiga toxin (Stx) 1 in human renal cortical epithelial cells (HRCECs), thereby protecting HRCECs from cell death. Further examination revealed that NBTI does not affect either the binding or the endocytosis of Stx1 but alters the intracellular transport of Stx1. Generally, endocytosed Stx1 is thought to be transported from endosomes to the endoplasmic reticulum. In NBTI-treated cells, however, the endocytosed Stx1 is delivered to an early endosome, but no further transportation occurs. Moreover, Stx1 is rapidly excreted from NBTI-treated HRCECs, preventing the accumulation of Stx1. Investigation of the NBTI-mediated protection mechanism against Stx cytotoxicity may provide insights into the analysis of Stx-mediated cell damage and lead to improvements in therapeutic approaches for diseases caused by Stx.