Regulatory volume decrease in Leishmania mexicana: effect of anti-microtubule drugs

Memórias do Instituto Oswaldo Cruz

Francehuli Dagger¹  Elizabeth Valdivieso¹  Ana K Marcano¹  Carlos Ayesta¹ 

[1],Universidad Central de Venezuela Facultad de Ciencias Instituto de Biología ExperimentalCaracas,Venezuela

关键词: microtubules;    drugs;    Leishmania;    regulatory volume decrease;   

DOI  :  10.1590/S0074-02762013000100014

来源: SciELO

【 摘 要 】

The trypanosomatid cytoskeleton is responsible for the parasite's shape and it is modulated throughout the different stages of the parasite's life cycle. When parasites are exposed to media with reduced osmolarity, they initially swell, but subsequently undergo compensatory shrinking referred to as regulatory volume decrease (RVD). We studied the effects of anti-microtubule (Mt) drugs on the proliferation of Leishmania mexicana promastigotes and their capacity to undergo RVD. All of the drugs tested exerted antiproliferative effects of varying magnitudes [ansamitocin P3 (AP3)> trifluoperazine > taxol > rhizoxin > chlorpromazine]. No direct relationship was found between antiproliferative drug treatment and RVD. Similarly, Mt stability was not affected by drug treatment. Ansamitocin P3, which is effective at nanomolar concentrations, blocked amastigote-promastigote differentiation and was the only drug that impeded RVD, as measured by light dispersion. AP3 induced 2 kinetoplasts (Kt) 1 nucleus cells that had numerous flagella-associated Kts throughout the cell. These results suggest that the dramatic morphological changes induced by AP3 alter the spatial organisation and directionality of the Mts that are necessary for the parasite's hypotonic stress-induced shape change, as well as its recovery.

【 授权许可】

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