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抗真菌及潜在抗肿瘤药物克霉唑诱导酿酒酵母BY4742中依赖半胱天冬酶的酵母凋亡。

Yeast caspase-dependent apoptosis in Saccharomyces cerevisiae BY4742 induced by antifungal and potential antitumor agent clotrimazole.

作者信息

Kavakçıoğlu Berna, Tarhan Leman

机构信息

Department of Chemistry, Faculty of Science, University of Dokuz Eylul, Tinaztepe Campus, 35160, Buca, Izmir, Turkey.

出版信息

Arch Microbiol. 2018 Jan;200(1):97-106. doi: 10.1007/s00203-017-1425-7. Epub 2017 Aug 17.

Abstract

Clotrimazole is an antifungal medication commonly used in the treatment of fungal infections. There is also promising research on using clotrimazole against other diseases such as malaria, beriberi, tineapedis and cancer. It was aimed to investigate the apoptotic phenotype in Saccharomyces cerevisiae induced by clotrimazole. The exposure of S. cerevisiae to 10 µM clotrimazole for 3, 6 and 9 h caused to decrease in cell viability by 24.82 ± 0.81, 56.00 ± 1.54 and 77.59 ± 0.53%, respectively. It was shown by Annexin V-PI assay that 110 µM clotrimazole treatment caused to death by 35.5 ± 2.48% apoptotic and only 13.1 ± 0.08% necrotic pathway within 30 min. The occurrence of DNA strand breaks and condensation could be visualised by the TUNEL and DAPI stainings, respectively. Yeast caspase activity was induced 12.34 ± 0.71-fold after 110 µM clotrimazole treatment for 30 min compared to the control. The dependency of clotrimazole-induced apoptosis to caspase was also shown using Δyca1 mutant.

摘要

克霉唑是一种常用于治疗真菌感染的抗真菌药物。关于使用克霉唑对抗其他疾病,如疟疾、脚气病、足癣和癌症,也有很有前景的研究。本研究旨在探讨克霉唑诱导酿酒酵母凋亡的表型。将酿酒酵母暴露于10 μM克霉唑中3小时、6小时和9小时,细胞活力分别下降了24.82±0.81%、56.00±1.54%和77.59±0.53%。Annexin V-PI分析表明,110 μM克霉唑处理在30分钟内导致35.5±2.48%的细胞通过凋亡途径死亡,仅13.1±0.08%的细胞通过坏死途径死亡。DNA链断裂和凝聚的发生分别可以通过TUNEL和DAPI染色观察到。与对照组相比,110 μM克霉唑处理30分钟后,酵母半胱天冬酶活性诱导了12.34±0.7-倍。使用Δyca1突变体也证明了克霉唑诱导的凋亡对半胱天冬酶的依赖性。

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