Genomewide expression profiling of cryptolepine-induced toxicity in Saccharomyces cerevisiae.

Antimicrobial Agents and Chemotherapy
Marta RojasJosé Portugal

Abstract

We have used the budding yeast Saccharomyces cerevisiae to identify genes that may confer sensitivity in vivo to the antimalarial and cytotoxic agent cryptolepine. Five S. cerevisiae strains, with different genetic backgrounds in cell permeability and DNA damage repair mechanisms, were exposed to several concentrations of cryptolepine. Cryptolepine showed a relatively mild toxicity for wild-type strains, which was augmented by either increasing cell permeability (Deltaerg6 or ISE2 strains) or disrupting DNA damage repair (Deltarad52 strains). These results are compatible with the ability of cryptolepine to intercalate into DNA and thus promote DNA lesions. The effects of low concentrations of cryptolepine (20% and 40% inhibitory concentrations [IC(20) and IC(40)]) were analyzed by comparing the gene expression profiles of treated and untreated Deltaerg6 yeast cells. Significant changes in expression levels were observed for 349 genes (117 upregulated and 232 downregulated). General stress-related genes constituted the only recognizable functional cluster whose expression was increased upon cryptolepine treatment, making up about 20% of upregulated genes. In contrast, analysis of the characteristics of downregulated genes reveal...Continue Reading

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Citations

Dec 22, 2009·Journal of Industrial Microbiology & Biotechnology·Lu YuXuming Deng
May 7, 2009·The Journal of Biological Chemistry·Combiz KhozoieSimon V Avery
Jul 14, 2010·Journal of Bioscience and Bioengineering·Daisuke Yasokawa, Hitoshi Iwahashi
Oct 1, 2009·IEEE Transactions on Information Technology in Biomedicine : a Publication of the IEEE Engineering in Medicine and Biology Society·Liping JingYing Liu

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