2016
DOI: 10.1038/srep36013
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Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae

Abstract: The mechanism of action of valproate (VPA), a widely prescribed short chain fatty acid with anticonvulsant and anticancer properties, remains poorly understood. Here, the yeast Saccharomyces cerevisiae was used as model to investigate the biological consequences of VPA exposure. We found that low pH strongly potentiates VPA-induced growth inhibition. Transcriptional profiling revealed that under these conditions, VPA modulates the expression of genes involved in diverse cellular processes including protein fol… Show more

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Cited by 9 publications
(7 citation statements)
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“…1), it is likely that the majority of the carbon utilized through glycolysis was converted to ethanol and not incorporated into anabolic pathways associated with cell growth and division. This is further supported by findings showing that VPA inhibited proliferation and cell cycle progression in yeast cells 51,57 .…”
Section: Discussionsupporting
confidence: 69%
“…1), it is likely that the majority of the carbon utilized through glycolysis was converted to ethanol and not incorporated into anabolic pathways associated with cell growth and division. This is further supported by findings showing that VPA inhibited proliferation and cell cycle progression in yeast cells 51,57 .…”
Section: Discussionsupporting
confidence: 69%
“…Cells expressing Rad52-YFP or Rfa1-YFP were fixed with formaldehyde as previously described [ 106 , 110 ] and stained with DAPI. Fluorescence was examined with a DeltaVision microscope equipped with SoftWorx version 6.2.0 software (GE Healthcare).…”
Section: Methodsmentioning
confidence: 99%
“…We have recently shown that low pH strongly potentiates VPA antimicrobial activity against the model yeast S. cerevisiae (Desfosses-Baron et al, 2016 ). Here, we investigated the in vitro susceptibility of both planktonic and sessile cells of different sensitive and resistant clinical isolates of the opportunistic yeast C. albicans to VPA using conditions mimicking the vaginal environment.…”
Section: Introductionmentioning
confidence: 99%
“…Despite the growing interest on VPA as antifungal, its precise mechanism of action remains not clear. Recent investigations in the budding yeast Saccharomyces cerevisiae have shown that VPA induces apoptosis and inhibits both cell-cycle at the G1-S transition and the activation of the cell wall integrity pathway, Stl2 MAP kinase (Mitsui et al, 2005 ; Desfosses-Baron et al, 2016 ). VPA was also shown to cause inositol depletion which in turn led to vacuolar ATPase perturbation (Ju and Greenberg, 2003 ; Deranieh et al, 2015 ).…”
Section: Introductionmentioning
confidence: 99%