Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C-mediated mechanism

Malgorzata Chalimoniuk, Kelley King-Pospisil, Ward A. Pedersen, Andrzej Malecki, Edward Wylegala, Mark P. Mattson, Bernhard Hennig, Michal J Toborek

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Arachidonic acid (AA) plays an important role as a signaling factor in the CNS. Therefore, exposure to AA may affect cholinergic neurons in the spinal cord. To test this hypothesis, mRNA expression and activity of choline acetyltransferase (ChAT) was measured in cultured spinal cord neurons treated with increasing concentrations (0.1-10 μM) of AA. Exposure to AA increased mRNA levels and activity of ChAT in dose- and time-dependent manners. The most marked effect of AA on ChAT expression was observed in spinal cord neurons treated with 10 μM AA for 1 h. To study the mechanisms associated with these effects, ChAT mRNA levels and activity were measured in cultured spinal cord neurons exposed to AA and inhibitors of protein kinase C (PKC), such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dichloride (H-7) and chelerythrine. Inhibition of PKC completely prevented an AA-induced increase in ChAT expression. In addition, exposure of spinal cord neurons to phorbol-12-myristate-13-acetate (PMA), an activator of PKC, mimicked AA-induced stimulation of ChAT activity. The AA-mediated increase in ChAT mRNA levels and activity was also prevented by treatments with EGTA, indicating the role of calcium metabolism in induction of this enzyme. In contrast, treatments with 7-nitroindazole (7-NI, a specific inhibitor of neuronal nitric oxide synthase), sodium vanadate (NaV, a non-specific inhibitor of phosphatases), and N-acetyl-cysteine (NAC, an antioxidant) had no effect on AA-induced changes in ChAT activity. The protein synthesis inhibitor cycloheximide completely blocked AA-mediated increase in ChAT activity. These results indicate that the AA-evoked increase in ChAT activity in spinal cord neurons is mediated by PKC, presumably at the transcriptional level.

Original languageEnglish
Pages (from-to)629-636
Number of pages8
JournalJournal of Neurochemistry
Volume90
Issue number3
DOIs
StatePublished - Aug 1 2004
Externally publishedYes

Fingerprint

Choline O-Acetyltransferase
Arachidonic Acid
Protein Kinase C
Neurons
Spinal Cord
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Messenger RNA
Acetylcysteine
Nitric Oxide Synthase Type I
Enzyme Induction
Cholinergic Neurons
Protein Synthesis Inhibitors
Vanadates
Egtazic Acid
Cycloheximide
Phosphoric Monoester Hydrolases
Metabolism
Cholinergic Agents
Cysteine
Acetates

Keywords

  • Arachidonic acid
  • Choline acetyltransferase
  • Protein kinase C
  • Spinal cord neurons

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C-mediated mechanism. / Chalimoniuk, Malgorzata; King-Pospisil, Kelley; Pedersen, Ward A.; Malecki, Andrzej; Wylegala, Edward; Mattson, Mark P.; Hennig, Bernhard; Toborek, Michal J.

In: Journal of Neurochemistry, Vol. 90, No. 3, 01.08.2004, p. 629-636.

Research output: Contribution to journalArticle

Chalimoniuk, Malgorzata ; King-Pospisil, Kelley ; Pedersen, Ward A. ; Malecki, Andrzej ; Wylegala, Edward ; Mattson, Mark P. ; Hennig, Bernhard ; Toborek, Michal J. / Arachidonic acid increases choline acetyltransferase activity in spinal cord neurons through a protein kinase C-mediated mechanism. In: Journal of Neurochemistry. 2004 ; Vol. 90, No. 3. pp. 629-636.
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