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 (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.
Sun
Qi
Q
Department of Biochemistry 2nd, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuou, Yamanashi 409-3898, Japan.
Bi
Lifu
L
Su
XiuLan
X
Tsurugi
Kunio
K
Mitsui
Kazuhiro
K
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017353:Gene Deletion; D006655:Histone Deacetylases / Q000172:deficiency / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008055:Lipids / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000172:deficiency / Q000378:metabolism*; D056565:Sirtuin 2; D037761:Sirtuins / Q000172:deficiency / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D008055:Lipids; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D014635:Valproic Acid; C499673:HDA1 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases