Confocal microscopic investigation of tubulin distribution and effect of paclitaxel on posttranslationally modified tubulins in sodium arsenite resistant Leishmania donovani.
The affinity of arsenic towards the cytoskeleton leading to disturbance of tubulin polymerization is well known. Tubulin undergoes extensive posttranslational modifications which effect stability and dynamics of microtubules but little is known about the effect of antimicrotubule drugs on their distribution and function in kinetoplastid parasites such as Leishmania. The current study was undertaken to investigate the effect of continuous sodium arsenite exposure on the tubulin distribution profile in wild type and sodium arsenite resistant Leishmania donovani together with effect of paclitaxel, a tubulin-polymerizing agent, on that distribution using confocal microscopy. Immunofluorescence studies using specific monoclonal antibodies against alpha-tubulin and posttranslationally modified tubulins (acetylated and tyrosinated) have revealed distinct differences in the organization of microtubule arrays in wild type and sodium arsenite resistant L. donovani that is further affected by paclitaxel treatment. Microtubules are arranged in spiral arrays in wild type as compared to the longitudinal arrays in arsenite resistant L. donovani. The difference in microtubular structure organization may explain the parasite response to continuous drug pressure and illustrate the fundamental impact of arsenite on microtubules in arsenite resistant L. donovani.
Chavan
Hemantkumar D
HD
Department of Biotechnology, National Institute of Pharmaceutical Education and Research(1), Sector 67, SAS Nagar, Punjab, India.
Singh
Gaganmeet
G
Dey
Chinmoy S
CS
D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D004351:Drug Resistance; D005455:Fluorescent Antibody Technique; D007893:Leishmania donovani / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D017239:Paclitaxel / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D017670:Sodium Compounds / Q000494:pharmacology; D014404:Tubulin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology*
D018053:Arsenites; D017670:Sodium Compounds; D014404:Tubulin; D050257:Tubulin Modulators; C017947:sodium arsenite; D017239:Paclitaxel