丙戊酸盐通过诱导中性脂质积累来诱导细胞凋亡，而在酿酒酵母中，SIR2基因的破坏可阻止这种积累。

Valproate induces apoptosis by inducing accumulation of neutral lipids which was prevented by disruption of the SIR2 gene in Saccharomyces cerevisiae.

作者信息

Sun Qi, Bi Lifu, Su XiuLan, Tsurugi Kunio, Mitsui Kazuhiro

机构信息

Department of Biochemistry 2nd, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuou, Yamanashi 409-3898, Japan.

出版信息

FEBS Lett. 2007 Aug 21;581(21):3991-5. doi: 10.1016/j.febslet.2007.07.030. Epub 2007 Jul 25.

DOI:10.1016/j.febslet.2007.07.030

PMID:17673205

Abstract

We investigated the participation of HDACs in VPA induced apoptosis in Saccharomyces cerevisiae. VPA (20 mM) induced apoptosis in several HDAC mutants, including PRD3 and HDA1-disrupted cells and SIR2 over expressing cells, as well as in wild-type cells but not SIR2-disrupted cells. Intracellular reactive oxygen species and neutral lipid content increased markedly in all kinds of HDAC mutant cells tested except for SIR2-disrupted cells. Thus, these results suggest that 20 mM VPA induces neutral lipid accumulation and apoptosis-like features in S. cerevisiae, and that VPA-induced apoptosis was evaded by deletion of SIR2.

摘要

我们研究了组蛋白去乙酰化酶（HDACs）在丙戊酸（VPA）诱导的酿酒酵母细胞凋亡中的作用。VPA（20 mM）可诱导包括PRD3和HDA1基因敲除细胞、SIR2过表达细胞以及野生型细胞在内的多种HDAC突变体细胞发生凋亡，但SIR2基因敲除细胞除外。除SIR2基因敲除细胞外，在所有测试的HDAC突变体细胞中，细胞内活性氧和中性脂质含量均显著增加。因此，这些结果表明，20 mM VPA可诱导酿酒酵母细胞中性脂质积累和凋亡样特征，且SIR2基因缺失可避免VPA诱导的细胞凋亡。