Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro

Guang Chen, Husseini K. Manji, David B. Hawver, Clinton B Wright, William Z. Potter

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. In view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to "therapeutic" concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme-selective decreases in the levels of PKC α and ∈ (but not δ or ζ) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or 3H-phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross-talk between neurotransmitter systems, the specific decreases in PKC γ and ∈ may play a role in the antimanic effects of VPA.

Original languageEnglish
Pages (from-to)2361-2364
Number of pages4
JournalJournal of Neurochemistry
Volume63
Issue number6
StatePublished - Dec 1 1994
Externally publishedYes

Fingerprint

Valproic Acid
Protein Kinase C
Antimanic Agents
Membranes
Isoenzymes
Signal transduction
In Vitro Techniques
Phorbol Esters
Lithium
Glioma
Anticonvulsants
Cytosol
Neurotransmitter Agents
Rats
Signal Transduction
Membrane Proteins
Fatty Acids
Western Blotting
Enzymes
Therapeutics

Keywords

  • Anticonvulsant
  • Manic-depressive illness
  • Protein kinase C
  • Valproate
  • Valproic acid

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Chen, G., Manji, H. K., Hawver, D. B., Wright, C. B., & Potter, W. Z. (1994). Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro. Journal of Neurochemistry, 63(6), 2361-2364.

Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro. / Chen, Guang; Manji, Husseini K.; Hawver, David B.; Wright, Clinton B; Potter, William Z.

In: Journal of Neurochemistry, Vol. 63, No. 6, 01.12.1994, p. 2361-2364.

Research output: Contribution to journalArticle

Chen, G, Manji, HK, Hawver, DB, Wright, CB & Potter, WZ 1994, 'Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro', Journal of Neurochemistry, vol. 63, no. 6, pp. 2361-2364.
Chen G, Manji HK, Hawver DB, Wright CB, Potter WZ. Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro. Journal of Neurochemistry. 1994 Dec 1;63(6):2361-2364.
Chen, Guang ; Manji, Husseini K. ; Hawver, David B. ; Wright, Clinton B ; Potter, William Z. / Chronic sodium valproate selectively decreases protein kinase C α and ∈ in vitro. In: Journal of Neurochemistry. 1994 ; Vol. 63, No. 6. pp. 2361-2364.
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