Valproate activates the Snf1 kinase in Saccharomyces cerevisiae by decreasing the cytosolic pH.

Adenosine Triphosphate / genetics Cytosol / enzymology Enzyme Activation / drug effects Glycolysis / drug effects Hydrogen-Ion Concentration Protein Serine-Threonine Kinases / genetics Proton-Translocating ATPases / genetics Saccharomyces cerevisiae / enzymology Saccharomyces cerevisiae Proteins / genetics Valproic Acid / pharmacology
Pma1 H(+)-ATPase SNF1/AMPK bipolar disorder cytosolic pH glycolysis inositol 1,4,5-triphosphate mitochondrial membrane potential valproate weak acid preservatives

Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
10 2021
Historique:
received: 30 03 2021
revised: 19 08 2021
accepted: 20 08 2021
pubmed: 25 8 2021
medline: 25 11 2021
entrez: 24 8 2021
Statut: ppublish

Résumé

Valproate (VPA) is a widely used mood stabilizer, but its therapeutic mechanism of action is not understood. This knowledge gap hinders the development of more effective drugs with fewer side effects. Using the yeast model to elucidate the effects of VPA on cellular metabolism, we determined that the drug upregulated expression of genes normally repressed during logarithmic growth on glucose medium and increased levels of activated (phosphorylated) Snf1 kinase, the major metabolic regulator of these genes. VPA also decreased the cytosolic pH (pH

Identifiants

DOI: 10.1016/j.jbc.2021.101110 PMID: 34428448 PMC: PMC8449051
pubmed: 34428448
pii: S0021-9258(21)00913-3
doi: 10.1016/j.jbc.2021.101110
pmc: PMC8449051
pii:
doi:

Substances chimiques

Saccharomyces cerevisiae Proteins 0
Valproic Acid 614OI1Z5WI
Adenosine Triphosphate 8L70Q75FXE
SNF1-related protein kinases EC 2.7.1.-
Protein Serine-Threonine Kinases EC 2.7.11.1
PMA1 protein, S cerevisiae EC 3.6.1.-
Proton-Translocating ATPases EC 3.6.3.14

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

101110

Subventions

Organisme : NCI NIH HHS
ID : P30 CA022453
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM125082
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM126020
Pays : United States

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

Auteurs

Michael Salsaa (M)

Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA.

Kerestin Aziz (K)

Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA.

Pablo Lazcano (P)

Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA.

Michael W Schmidtke (MW)

Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA.

Maureen Tarsio (M)

Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York, USA.

Maik Hüttemann (M)

Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, Michigan, USA.

Christian A Reynolds (CA)

Department of Emergency Medicine, School of Medicine, Wayne State University, Detroit, Michigan, USA; Department of Biotechnology, University of Rijeka, Rijeka, Croatia.

Patricia M Kane (PM)

Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, New York, USA.

Miriam L Greenberg (ML)

Department of Biological Sciences, Wayne State University, Detroit, Michigan, USA. Electronic address: mgreenberg@wayne.edu.

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Classifications MeSH

questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléotides › Ribonucléotides › Nucléotides adényliques › Adénosine triphosphate › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Cellules › Structures cellulaires › Fractions subcellulaires › Cytosol › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Métabolisme › Activation enzymatique › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Phénomènes chimiques › Concentration en ions d'hydrogène › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs de cations › Pompes à protons › Proton-Translocating ATPases › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Saccharomyces › Saccharomyces cerevisiae › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Protéines de Saccharomyces cerevisiae › Valproate activates the Snf1 kinase in...
questionsmedicales.fr › Lipides › Acides gras › Acides gras volatils › Valérates › Acides pentanoïques › Acide valproïque › Valproate activates the Snf1 kinase in...