Effect of clotrimazole on cytosolic Ca2+ rise and viability in HA59T human hepatoma cells
| Autor: | Peng-Chih-Tsai, 蔡朋志 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Clotrimazole is an antimycotic imidazole derivative that interferes with cellular Ca2+ homeostasis. This study examined the effect of clotrimazole on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in HA59T human hepatoma cells. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Clotrimazole induced [Ca2+]i rises in a concentration-dependent manner. The response was reduced by removing extracellular Ca2+. Clotrimazole-evoked Ca2+ entry was suppressed by store-operated channel inhibitors (nifedipine, econazole and SK&F96365) and protein kinase C modulators (GF109203X and phorbol 12-myristate 13-acetate). In Ca2+-free medium, incubation with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished clotrimazole-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 abolished clotrimazole-induced [Ca2+]i rise. At 10-40 M, clotrimazole inhibited cell viability, which was not reversed by chelating cytosolic Ca2+. Clotrimazole at 10 and 30 M also induced apoptosis. Collectively, in HA59T cells, clotrimazole induced [Ca2+]i rises by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via store-operated Ca2+ channels. Clotrimazole also caused apoptosis. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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