School of Life Sciences, Anhui Agricultural University, Hefei, China.
FEMS Yeast Res. 2013 Dec;13(8):796-803. doi: 10.1111/1567-1364.12089. Epub 2013 Oct 3.
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.
胆固醇氧化产物的细胞毒性已在几种哺乳动物细胞系中得到证实。它可导致多种疾病。然而，这种毒性在体内的分子机制却很少。本研究的目的是评估 7-酮胆固醇（一种重要的胆固醇氧化产物）对酿酒酵母的潜在毒性作用。我们的数据首次表明，7-酮胆固醇可诱导酿酒酵母中剂量依赖性的细胞死亡。这些结果表明，该化合物诱导的死亡是凋亡，并伴有染色质浓缩、ROS 的产生以及磷脂酰丝氨酸从细胞质膜的内层到外层的易位。我们进一步表明，用半胱氨酸天冬氨酸蛋白酶抑制剂（Z-VAD-fmk）预处理后，7-酮胆固醇诱导的细胞死亡部分得到挽救。此外，半胱氨酸天冬氨酸蛋白酶缺失导致细胞活力增加。所有这些结果都强烈表明，7-酮胆固醇通过半胱氨酸天冬氨酸蛋白酶依赖性途径诱导酵母细胞凋亡。
