Epileptogenesis in diacylglycerol kinase epsilon deficiency up-regulates COX-2 and tyrosine hydroxylase in hippocampus

Walter J. Lukiw, Jian Guo Cui, Alberto E. Musto, Brenda C. Musto, Nicolas G. Bazan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Diacylglycerol kinase (DGK) phosphorylates the second messenger diacylglycerol (DAG) to yield phosphatidic acid, two neural signaling elements that function to modulate synaptic activity. Of the nine mammalian DGK isotypes known, DGK epsilon (DGKε) shows specificity for arachidonoyldiacylglycerol (20:4-DAG) and selectively contributes to modulate brain signaling pathways linked to synaptic activity and epileptic seizure activity. In this study, we examined changes in gene transcription in a mouse kindling model of epileptogenesis using control DGKε (+/+) and DGKε-knockout (-/-) mice. Total RNA was isolated from the hippocampus and analyzed using RNA and DNA arrays. Significantly altered gene-expression levels were confirmed independently using Western immunoblot analysis. In agreement with our previous studies, a very few number of genes reached a significance of twofold or greater (either up- or down-regulated; p < 0.05). Among the most significantly up-regulated genes in DGKε (+/+) mice included those encoding the inducible prostaglandin synthase cyclooxygenase-2 (COX-2) and tyrosine hydroxylase (TH), also known as tyrosine 3-monooxygenase, the rate-limiting enzyme of catecholamine biosynthesis. Kindled DGKε (-/-) animals exhibited no large increases in COX-2 or TH gene expression. These data, plus our previous findings that DGKε (-/-) mice show higher resistance to electroconvulsive shock, suggest an interplay between and regulatory role for DGKε, COX-2, and catecholamine signaling during kindling epileptogenesis.

Original languageEnglish (US)
Pages (from-to)77-81
Number of pages5
JournalBiochemical and biophysical research communications
Volume338
Issue number1
DOIs
StatePublished - Dec 9 2005

Keywords

  • Cyclooxygenase-2
  • Diacylglycerol kinase epsilon
  • Epilepsy
  • Gene expression
  • Kindling epileptogenesis
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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