7-ketocholesterol-induced caspase-mediated apoptosis in Saccharomyces cerevisiae

Qiulin Yue1, Xiuhong Zhou, Qianli Leng

  • 1School of Life Sciences, Anhui Agricultural University, Hefei, China.

FEMS Yeast Research
|September 14, 2013
PubMed

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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