Increased calcium permeability is not responsible for the rapid lethal effects of amphotericin B on Leishmania sp

FEBS Letters

Michelangeli, Fabián²  Ruiz, Marie-Christine¹  Benaim, Gustavo²  Cohen, B.Eleazar² 

[1] Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela;Centro de Biologia Celular, Facultad de Ciencias, Universidad Central de Venezuela, Apartado 47860, Caracas 1041 Venezuela

关键词: Amphotericin B;    Polyene antibiotic;    Calcium;    Leishmania;    Quin-2;    Ethidium bromide;   

DOI  :  10.1016/0014-5793(90)80028-H

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mode of action of the polyene antibiotic amphotericin B (AmB), the drug of choice for the treatment of systemic fungal infections and visceral leishmaniasis, is still unclear. An increase in intracellular Ca²⁺ concentration ([Ca²⁺]_i), toxic in many cases, has been postulated as a possible lethal mechanism for AmB. Cell permeabilization to ethidium bromide (EB) was used as a criterion of viability. Kinetics of the DNA-EB fluorescent complex formation was studied in ergosterol-containing Leishmania promastigotes. Intracellular Ca²⁺ concentration was measured using quin-2 fluorescence in parallel aliquots. It is shown in this work that AmB can act as an efficient Ca²⁺ ionophore. However, the rapid permeabilization effect induced by AmB on these cells was not dependent on an increase in [Ca²⁺]_i. On the contrary, it was found that leishmanicidal effect of AmB was enhanced in the absence of external calcium. Furthermore, A23187 a Ca²⁺ ionophore did not provoke cell penneabilization to EB.

【 授权许可】

Unknown