Mechanisms involved in prostaglandin E2-mediated neuroprotection against TNF-α: possible involvement of multiple signal transduction and β-catenin/T-cell factor

Lee, Eun Ok; Shin, Yoo Jung; Chong, Young Hae

doi:10.1016/j.jneuroim.2004.05.012

Cited by 52 publications

(29 citation statements)

References 48 publications

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“…PGE 2 was reported to protect against apoptosis in several cell types, including bone-marrow-derived and monocyte-de- rived dendritic cells [10,31], neurons [32], epithelial cells, and colon cancer cells [12,34]. However, PGE 2 was also reported to induce apoptosis in articular chondrocytes and hippocampal neurons [33,34].…”

Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

et al. 2007

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Little is known about prostaglandin synthesis and function in embryonic stem cells. We postulated that mouse embryonic stem (mES) cells possess enzymes to synthesize protective prostaglandins. Compared with differentiated adult cells, mES cells were less susceptible to H 2 O 2 -induced apoptosis. However, their apoptosis was enhanced by indomethacin or SC-236, a selective inhibitor of cyclooxygenase (COX)-2. Analysis of COX pathway enzymes by Western blotting revealed expression of COX-2 and cytosolic and microsomal prostaglandin E 2 (PGE 2 ) synthases. COX-1 and prostacyclin (PGI 2 ) synthases were undetectable. mES cells produced PGE 2 but not PGI 2 . Importantly, PGE 2 rescued mES cells from apoptosis. To elucidate the signaling mechanism by which PGE 2 inhibits apoptosis, we analyzed E-type prostaglandin (EP) receptors by Western blots. All EP isoforms were detected except EP4. Butaprost, a specific EP2 agonist, rescued mES cells from apoptosis, whereas sulprostone, an EP1/EP3 agonist, had no effect, suggesting selective interaction of PGE 2 with EP2. The antiapoptotic effect of PGE 2 was abrogated by Ly-294002 or wortmannin but not H-89 or a specific inhibitor of protein kinase A, suggesting signaling via phosphatidylinositol-3 kinase (PI-3K). Akt was constitutively active in mES cells, which were inhibited by indomethacin and rescued by PGE 2 . The rescuing effect of PGE 2 was abrogated by Ly-294002. These results indicate that mES cells constitutively express COX-2 and PGE synthases and produce PGE 2 , which confers resistance to apoptosis via EP2-mediated activation of PI-3K to the Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

et al. 2007

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“…The EP2 receptor promotes protection in a chronic model of excitotoxic motor neuron degeneration, 14 and in amyloid-␤ 18 and inflammatory 19,20 neurotoxicity. Taken together, these data support the investigation of therapeutic strategies that target the PGE 2 EP2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by the PGE₂ EP2 receptor in permanent focal cerebral ischemia

Liu

Breyer

et al. 2005

Annals of Neurology

124

125

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Recent studies suggest a neuroprotective function of the PGE2 EP2 receptor in excitotoxic neuronal injury. The function of the EP2 receptor was examined at time points after excitotoxicity in an organotypic hippocampal model of N-methyl-D-aspartate (NMDA) challenge and in a permanent model of focal forebrain ischemia. Activation of EP2 led to significant neuroprotection in hippocampal slices up to 3 hours after a toxic NMDA stimulus. Genetic deletion of EP2 resulted in a marked increase in stroke volume in the permanent middle cerebral artery occlusion model. These findings support further investigation into therapeutic strategies targeting the EP2 receptor in stroke.

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“…1C). PKB/ Akt-mediated phosphorylation of GSK-3b was again found to be a central mechanism, 45 although PKA 44,46,47 and even PKCs 46 were reported to be involved. In the case of EP 2 and EP 4 receptors for PGE 2 , the mechanisms appeared to be mediated by PKA-dependent (Ga s -linked EP 2 receptor) or PI3-K-dependent (Ga q -linked EP 4 receptor) inhibition of GSK-3b.…”

Section: Mechanisms Of Activation Of B-catenin By Heterotrimeric G Prmentioning

confidence: 99%

Activation of β-catenin Signaling Pathways by Classical G-Protein-Coupled Receptors: Mechanisms and Consequences in Cycling and Non-cycling Cells

Shevtsov¹,

Haq²,

Force³

2006

Cell Cycle

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Wnt signaling pathways are some of the most intensely studies in all of biology. Recently, a number of classical heterotrimeric G protein coupled receptors (GPCRs) have been shown to activate the canonical Wnt pathway, culminating in the stabilization of b-catenin and induction of transcription of genes regulated by the Tcf/Lef family of transactivators. However, mechanisms by which these GPCRs accomplish this differ in key ways, and in some circumstances, the phenotypes produced are novel. Herein, we will examine mechanisms by which classical GPCRs interact with the canonical Wnt pathway, culminating in its activation, and describe the consequences of this activation, focusing on the heart. In the heart, the contractile cells, or cardiomyocytes, are terminally differentiated and virtually exclusively grow by increasing cell size (hypertrophy) rather than cell number, and we will describe how GPCR-mediated activation of the canonical pathway can drive this process.

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Mechanisms involved in prostaglandin E2-mediated neuroprotection against TNF-α: possible involvement of multiple signal transduction and β-catenin/T-cell factor

Cited by 52 publications

References 48 publications

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

Neuroprotection by the PGE₂ EP2 receptor in permanent focal cerebral ischemia

Activation of β-catenin Signaling Pathways by Classical G-Protein-Coupled Receptors: Mechanisms and Consequences in Cycling and Non-cycling Cells

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Mechanisms involved in prostaglandin E2-mediated neuroprotection against TNF-α: possible involvement of multiple signal transduction and β-catenin/T-cell factor

Cited by 52 publications

References 48 publications

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

Neuroprotection by the PGE2 EP2 receptor in permanent focal cerebral ischemia

Activation of β-catenin Signaling Pathways by Classical G-Protein-Coupled Receptors: Mechanisms and Consequences in Cycling and Non-cycling Cells

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Neuroprotection by the PGE₂ EP2 receptor in permanent focal cerebral ischemia