title: 7-ketocholesterol-induced caspase-mediated apoptosis in Saccharomyces cerevisiae.
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.
authors.affiliation: School of Life Sciences, Anhui Agricultural University, Hefei, China.
authors.forename: Qiulin
authors.initials: Q
authors.lastname: Yue
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Zhou
authors.forename: Qianli
authors.initials: Q
authors.lastname: Leng
authors.forename: Lele
authors.initials: L
authors.lastname: Zhang
authors.forename: Beijiu
authors.initials: B
authors.lastname: Cheng
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D007653:Ketocholesterols / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D007653:Ketocholesterols; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C443623:AIF1 protein, S cerevisiae; D009247:NADH, NADPH Oxidoreductases; D020169:Caspases; C456272:MCA1 protein, S cerevisiae; C003001:7-ketocholesterol
keywords: 7-ketocholesterol; Saccharomyces cerevisiae; apoptosis; cholesterol oxidation products