The dual mechanism of the antifungal effect of new lysosomotropic agents on the Saccharomyces cerevisiae RXII strain

• Autorzy: Krasowska A , Chmielewska L. , Luczynski J. , Witek S. , Sigler K.
• Języki publikacji: EN

Abstrakty

EN

Quinacrine was used to visualize the intracellular pH changes in the yeast strain Saccharomyces cerevisiae RXII occurring after exposure to four recently-synthesized lysosomotropic drugs: DM-11, PY-11, PYG-12s and DMAL-12s. The cells took up quinacrine, mostly accumulating it in their vacuoles. DM-11 and PY-11 gave rise to diffuse quinacrine fluorescence throughout the cells, with the vacuoles staining to a somewhat greater extent than the cytosol. This quinacrine-detected overall acidification of the cell interior is very probably caused by blocking of plasma membrane H+-ATPase. PYG-12s gave rise to a strong vacuolar accumulation of the dye. Like the vacuolar ATPase inhibitor bafilomycin A1, DMAL-12s strongly lowered the intensity of quinacrine fluorescence. Owing to its low pKa, it can penetrate rapidly into the cells and may inhibit vacuolar H+-ATPase and prevent quinacrine-detectable vacuolar acidification without causing strong cell acidification. Since these drugs were found to penetrate into the cells, their lack of effect may reflect a higher resistance of both plasma membrane H+-ATPase and vacuolar ATPase to the drugs. Our data indicate that the lysosomotropic drugs under study have a dual action. On entering the cell, they cause intracellular acidification, very probably by inhibiting plasma membrane H+-ATPase and curtailing active proton pumping from the cells. Furthermore, they interfere with the function of V-type ATPase, causing vacuolar alkalinization and eventually cell death.

Słowa kluczowe

EN

yeast; pH change; antifungal effect; lysosomotropic agent; Saccharomyces cerevisiae

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 2003
• Tom: 08
• Numer: 1
• Opis fizyczny: p.111-120,fig.

Twórcy

autor

Krasowska A

• Wroclaw University, Przybyszewskiego 63-77, 51-148 Wroclaw, Poland

autor

Chmielewska L.

autor

Luczynski J.

autor

Witek S.

autor

Sigler K.

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