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7-ketocholesterol-induced caspase-mediated apoptosis in Saccharomyces cerevisiae
Qiulin Yue1, Xiuhong Zhou, Qianli Leng
1School of Life Sciences, Anhui Agricultural University, Hefei, China.
Abstract:
The cytotoxicity of cholesterol oxidation products has been documented in several mammalian cell lines. It can lead to a wide range of diseases. However, the molecular mechanisms underlying this toxicity in vivo are scarce. The objective of the present study was to assess the potential toxic effects of 7-ketocholesterol, an important cholesterol oxidation product, on Saccharomyces cerevisiae. Our data show for the first time that 7-ketocholesterol can induce dose-dependent cell death in S. cerevisiae. These results suggest that the death induced by this compound is apoptotic and accompanied by chromatin condensation, the production of ROS, and translocation of phosphatidylserine from the inner to the outer leaflet of the cytoplasmic membrane. We further showed that 7-ketocholesterol-induced cell death was partially rescued after pretreatment with caspase inhibitor (Z-VAD-fmk). In addition, caspase deletion resulted in promotion of cell viability. All these results strongly indicated that 7-ketocholesterol induces apoptosis in yeast cells through a caspase-dependent pathway.
Insights
7-ketocholesterol, a cholesterol oxidation product, induces programmed cell death (apoptosis) in yeast cells. This process involves reactive oxygen species and caspase activation, offering insights into its toxicity mechanisms.
Area of Science:
- Biochemistry
- Cell Biology
- Toxicology
Background:
- Cholesterol oxidation products exhibit cytotoxicity in mammalian cells, contributing to various diseases.
- The in vivo molecular mechanisms of this toxicity remain largely unelucidated.
Purpose of the Study:
- To investigate the toxic effects of 7-ketocholesterol, a key cholesterol oxidation product, on Saccharomyces cerevisiae.
- To elucidate the molecular pathways involved in 7-ketocholesterol-induced cell death in yeast.
Main Methods:
- Dose-dependent treatment of S. cerevisiae with 7-ketocholesterol.
- Assessment of cell death markers including chromatin condensation, reactive oxygen species (ROS) production, and phosphatidylserine translocation.
- Evaluation of caspase involvement using a caspase inhibitor (Z-VAD-fmk) and caspase deletion mutants.
Main Results:
- 7-ketocholesterol induced dose-dependent cell death in S. cerevisiae.
- The observed cell death exhibited characteristics of apoptosis, such as chromatin condensation, ROS generation, and phosphatidylserine externalization.
- 7-ketocholesterol-induced apoptosis was partially inhibited by a caspase inhibitor and significantly reduced in caspase-deficient yeast strains.
Conclusions:
- 7-ketocholesterol triggers apoptosis in yeast cells.
- This apoptotic process is mediated through a caspase-dependent pathway.
- Saccharomyces cerevisiae serves as a valuable model for studying the toxic mechanisms of cholesterol oxidation products.
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