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