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 Citations (Scopus)

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
Pages (from-to)77-81
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume338
Issue number1
DOIs
StatePublished - Dec 9 2005

Fingerprint

Diacylglycerol Kinase
Tyrosine 3-Monooxygenase
Cyclooxygenase 2
Hippocampus
Up-Regulation
Genes
Diglycerides
Prostaglandin-Endoperoxide Synthases
Gene expression
Catecholamines
2-tyrosine
RNA
Gene Expression
Electroshock
Phosphatidic Acids
Biosynthesis
Second Messenger Systems
Transcription
Oligonucleotide Array Sequence Analysis
Knockout Mice

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Epileptogenesis in diacylglycerol kinase epsilon deficiency up-regulates COX-2 and tyrosine hydroxylase in hippocampus. / Lukiw, Walter J.; Cui, Jian Guo; Musto, Alberto E.; Musto, Brenda C.; Bazan, Nicolas G.

In: Biochemical and Biophysical Research Communications, Vol. 338, No. 1, 09.12.2005, p. 77-81.

Research output: Contribution to journalArticle

Lukiw, Walter J. ; Cui, Jian Guo ; Musto, Alberto E. ; Musto, Brenda C. ; Bazan, Nicolas G. / Epileptogenesis in diacylglycerol kinase epsilon deficiency up-regulates COX-2 and tyrosine hydroxylase in hippocampus. In: Biochemical and Biophysical Research Communications. 2005 ; Vol. 338, No. 1. pp. 77-81.
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