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

We investigated the participation of HDACs in VPA induced apoptosis in Saccharomyces cerevisiae. VPA (20mM) 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 rea...

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Bibliographic Details
Published in:FEBS letters 2007-08, Vol.581 (21), p.3991-3995
Main Authors: Sun, Qi, Bi, Lifu, Su, XiuLan, Tsurugi, Kunio, Mitsui, Kazuhiro
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Budding yeast
Enzyme Inhibitors - pharmacology
Gene Deletion
HDAC
histone deacetylase
Histone Deacetylases - deficiency
Histone Deacetylases - metabolism
Lipid accumulation
Lipid Metabolism - drug effects
Lipid Metabolism - physiology
Lipids - physiology
reactive oxygen species
Reactive Oxygen Species - metabolism
ROS
Saccharomyces cerevisiae
Saccharomyces cerevisiae - enzymology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins - metabolism
Silent Information Regulator Proteins, Saccharomyces cerevisiae - deficiency
Silent Information Regulator Proteins, Saccharomyces cerevisiae - metabolism
SIR2
Sirtuin 2
Sirtuins - deficiency
Sirtuins - metabolism
TAG
triacylglycerol
Valproate
valproic acid
Valproic Acid - pharmacology
VPA
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Summary:We investigated the participation of HDACs in VPA induced apoptosis in Saccharomyces cerevisiae. VPA (20mM) 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 20mM VPA induces neutral lipid accumulation and apoptosis-like features in S. cerevisiae, and that VPA-induced apoptosis was evaded by deletion of SIR2.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2007.07.030