Epileptogenesis in diacylglycerol kinase epsilon deficiency up-regulates COX-2 and tyrosine hydroxylase in hippocampus.
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 (DGKepsilon) 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 DGKepsilon (+/+) and DGKepsilon-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 DGKepsilon (+/+) 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 DGKepsilon (-/-) animals exhibited no large increases in COX-2 or TH gene expression. These data, plus our previous findings that DGKepsilon (-/-) mice show higher resistance to electroconvulsive shock, suggest an interplay between and regulatory role for DGKepsilon, COX-2, and catecholamine signaling during kindling epileptogenesis.
Lukiw
Walter J
WJ
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine in New Orleans, LA 70112, USA.
Cui
Jian-Guo
JG
Musto
Alberto E
AE
Musto
Brenda C
BC
Bazan
Nicolas G
NG
D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D019852:Diacylglycerol Kinase / Q000172:deficiency* / Q000235:genetics; D004827:Epilepsy / Q000201:enzymology* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics*
D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D051546:Cyclooxygenase 2; D019852:Diacylglycerol Kinase