Altered expression, polymerisation and cellular distribution of alpha-/beta-tubulins and apoptosis-like cell death in arsenite resistant Leishmania donovani promastigotes.
Studies in mammalian systems have shown specific affinity of arsenite for tubulin proteins. The sodium m-arsenite (NaAsO2) resistant Leishmania donovani used in this study is resistant to 20 microM NaAsO2, which is a 13-fold increase in resistance compared to the wild type. Data presented in this study shows decreased expression of alpha- and beta-tubulin in wild type L. donovani promastigotes on exposure to NaAsO2 from 0.0016 to 5.0 microM (IC50 in the wild type strain) in a dose-dependent manner. alpha- and beta-tubulins in the resistant strain show decreased expression levels only at 65.0 microM NaAsO2 (IC50 in the resistant strain). Treatment with respective IC50 concentrations of NaAsO2 caused alterations in tubulin polymerisation dynamics and deregulated the cellular distribution of the microtubules in wild type and resistant strains. The NaAsO2-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.
Jayanarayan
K G
KG
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S Nagar, Punjab 160062, India.
Dey
Chinmoy S
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D018053:Arsenites / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D003470:Culture Media; D053938:DNA Fragmentation / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D017670:Sodium Compounds / Q000494:pharmacology*; D012995:Solubility; D014404:Tubulin / Q000032:analysis* / Q000235:genetics
D018053:Arsenites; D003470:Culture Media; D016054:DNA, Protozoan; D004791:Enzyme Inhibitors; D011108:Polymers; D017670:Sodium Compounds; D014404:Tubulin; C017947:sodium arsenite; D011065:Poly(ADP-ribose) Polymerases