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

Lukiw, Walter J.; Cui, Jian; Musto, Alberto E.; Musto, Brenda C.; Bazán, Nicolás G.

doi:10.1016/j.bbrc.2005.08.109

Cited by 20 publications

(16 citation statements)

References 20 publications

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“…Thus DGKe may also be involved in another function to increase enrichment of arachidonoyl content during the conversion of PA to PI (Milne et al, 2008) which we are currently investigating. shown to reduce levels of free arachidonic acid, 20:4-DAG, and 20:4-PI(4,5)P 2 in response to electroconvulsive shock (Lukiw et al, 2005;Musto and Bazan, 2006;Bazan, 2005). These lipids serve several important biological functions and their dysregulation is implicated in a range of diseased states.…”

Section: Dgke and The Pi-cyclementioning

confidence: 97%

Molecular properties of diacylglycerol kinase-epsilon in relation to function

Jennings

Doshi

D’Souza

et al. 2015

Chemistry and Physics of Lipids

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Section: Dgke and The Pi-cyclementioning

confidence: 97%

Molecular properties of diacylglycerol kinase-epsilon in relation to function

Jennings

Doshi

D’Souza

et al. 2015

Chemistry and Physics of Lipids

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“…DGK -null mice exhibit several neural abnormalities, including a higher resistance of electroconvulsive shock ( 5 ) and increased cyclooxygenase 2 and tyrosine hydroxylase expression ( 6 ), suggesting a role for DGK in regulating synaptic activity. Mice lacking DGK ␣ ( 7 ) or DGK ( 8 ) exhibit enhanced T cell function and demonstrate a role for these kinases in controlling DAG metabolism during the immune response.…”

mentioning

confidence: 99%

cAMP-stimulated transcription of DGKθ requires steroidogenic factor 1 and sterol regulatory element binding protein 1

Cai

Sewer

2013

Journal of Lipid Research

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( 4 ). DGK -null mice exhibit several neural abnormalities, including a higher resistance of electroconvulsive shock ( 5 ) and increased cyclooxygenase 2 and tyrosine hydroxylase expression ( 6 ), suggesting a role for DGK in regulating synaptic activity. Mice lacking DGK ␣ ( 7 ) or DGK ( 8 ) exhibit enhanced T cell function and demonstrate a role for these kinases in controlling DAG metabolism during the immune response. DGK isoforms have been implicated in various other cellular processes including inhibition of Rap1 signaling ( 9 ) and retinoblastoma-mediated cell cycle control ( 10 ). DGK is activated by nerve growth factor in PC12 cells ( 11 ) and thrombin in IIC9 fi broblasts ( 12, 13 ), whereas DGK promotes myogenesis in C2C12 cells ( 14 ) and DGK ␥ plays a role in regulating the cell cycle in CHO-K cells ( 15 ).To date, 10 mammalian DGKs have been identifi ed that are divided into fi ve groups based on functional domains ( 16,17 ). However, all isoforms contain cysteine-rich zinc fi nger-like structures, a conserved catalytic region ( 18-21 ). DGK , the sole member of group V, is comprised of three cysteine-rich domains (CRDs), a proline/glycine-rich domain at its N terminus, and a pleckstrin homology (PH) with an overlapping Ras-binding domain ( 22 ). While the functions of many of the other domains in DGK are unclear, the catalytic activity requires all domains of the enzyme ( 23 ). It has been postulated that the CRDs of the enzyme are required both for correct folding of the protein and for substrate presentation ( 23 ). Mutation of the CRD of DGK diminishes DAG-induced translocation of the enzyme to the plasma membrane ( 24 ); whereas the interaction between DGK and the nuclear receptor steroidogenic factor 1 (SF1) requires the PH domain ( 25 ). Abstract Diacylglycerol kinase (DGK) is

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“…As the generation of new neurons or glia within the hippocampus is initiated by local signaling (Brock et al, 1998), alterations in the microenvironment such as microglial inflammation and the release of proinflammatory cytokines may affect normal cell proliferation and differentiation, which could cause ectopic neurogenesis, astrogliosis and ectopic synaptic reorganization (Jin et al, 2006). Cyclooxgenase-2 (COX-2), as a proinflammatory mediator encoded in an early-response gene, is induced by synaptic activity (Lukiw et al, 2005); therefore, COX-2 activity could contribute to epileptic neuronal injury.…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

Zhang

Sun

Lei

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms. Methods: Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of α-subunit of γ-amino butyric acid (GABA A ) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting. Results: Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABA A receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs. Conclusion: The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.

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

Cited by 20 publications

References 20 publications

Molecular properties of diacylglycerol kinase-epsilon in relation to function

Molecular properties of diacylglycerol kinase-epsilon in relation to function

cAMP-stimulated transcription of DGKθ requires steroidogenic factor 1 and sterol regulatory element binding protein 1

Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats

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