Altered expression, polymerisation and cellular distribution of α-/β-tubulins and apoptosis-like cell death in arsenite resistant Leishmania donovani promastigotes

Abstract

Studies in mammalian systems have shown specific affinity of arsenite for tubulin proteins. The sodium m-arsenite (NaAsO 2) resistant Leishmania donovani used in this study is resistant to 20 μM NaAsO 2, which is a 13-fold increase in resistance compared to the wild type. Data presented in this study shows decreased expression of α- and β-tubulin in wild type L. donovani promastigotes on exposure to NaAsO 2 from 0.0016 to 5.0 μM (IC 50 in the wild type strain) in a dose-dependent manner. α- and β-tubulins in the resistant strain show decreased expression levels only at 65.0 μM NaAsO 2 (IC 50 in the resistant strain). Treatment with respective IC 50 concentrations of NaAsO 2 caused alterations in tubulin polymerisation dynamics and deregulated the cellular distribution of the microtubules in wild type and resistant strains. The NaAsO 2-induced cell death exhibited characteristics of apoptosis-like DNA laddering and fragmentation in both the affected wild type and resistant cells. However, poly(ADP-ribose)polymerase cleavage was evident in the wild type strain but not in the resistant strain.