Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus

Han Fang Wu, Yi Ju Chen, Su Zhen Wu, Chi Wei Lee, I. Tuan Chen, Yi Chao Lee, Chi Chen Huang, Chung Hsi Hsing, Chih Wei Tang, Hui Ching Lin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation-(HFS-) induced long-Term potentiation (LTP) and forskolin-(FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-Aspartate (NMDA) receptor subunit NR2B antagonist. TPPU-or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin-(CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR-and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus.

Original languageEnglish
Article number3467805
JournalNeural Plasticity
Volume2017
DOIs
Publication statusPublished - 2017

Fingerprint

Epoxide Hydrolases
Long-Term Potentiation
Cyclic AMP-Dependent Protein Kinases
Hippocampus
Extracellular Signal-Regulated MAP Kinases
Protein Kinases
Adenosine A1 Receptor Antagonists
Phosphorylation
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neurotransmitter Receptor
Acids
Phosphodiesterase Inhibitors
Excitatory Postsynaptic Potentials
Colforsin
Protein Kinase Inhibitors
Arachidonic Acid
Central Nervous System
14,15-epoxy-5,8,11-eicosatrienoic acid
Pharmacology

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus. / Wu, Han Fang; Chen, Yi Ju; Wu, Su Zhen; Lee, Chi Wei; Chen, I. Tuan; Lee, Yi Chao; Huang, Chi Chen; Hsing, Chung Hsi; Tang, Chih Wei; Lin, Hui Ching.

In: Neural Plasticity, Vol. 2017, 3467805, 2017.

Research output: Contribution to journalArticle

Wu, Han Fang ; Chen, Yi Ju ; Wu, Su Zhen ; Lee, Chi Wei ; Chen, I. Tuan ; Lee, Yi Chao ; Huang, Chi Chen ; Hsing, Chung Hsi ; Tang, Chih Wei ; Lin, Hui Ching. / Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus. In: Neural Plasticity. 2017 ; Vol. 2017.
@article{e629459088844ac6a1b812f76dca98d8,
title = "Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus",
abstract = "Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation-(HFS-) induced long-Term potentiation (LTP) and forskolin-(FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-Aspartate (NMDA) receptor subunit NR2B antagonist. TPPU-or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin-(CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR-and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus.",
author = "Wu, {Han Fang} and Chen, {Yi Ju} and Wu, {Su Zhen} and Lee, {Chi Wei} and Chen, {I. Tuan} and Lee, {Yi Chao} and Huang, {Chi Chen} and Hsing, {Chung Hsi} and Tang, {Chih Wei} and Lin, {Hui Ching}",
year = "2017",
doi = "10.1155/2017/3467805",
language = "English",
volume = "2017",
journal = "Neural Plasticity",
issn = "2090-5904",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Soluble Epoxide Hydrolase Inhibitor and 14,15-Epoxyeicosatrienoic Acid-Facilitated Long-Term Potentiation through cAMP and CaMKII in the Hippocampus

AU - Wu, Han Fang

AU - Chen, Yi Ju

AU - Wu, Su Zhen

AU - Lee, Chi Wei

AU - Chen, I. Tuan

AU - Lee, Yi Chao

AU - Huang, Chi Chen

AU - Hsing, Chung Hsi

AU - Tang, Chih Wei

AU - Lin, Hui Ching

PY - 2017

Y1 - 2017

N2 - Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation-(HFS-) induced long-Term potentiation (LTP) and forskolin-(FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-Aspartate (NMDA) receptor subunit NR2B antagonist. TPPU-or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin-(CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR-and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus.

AB - Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation-(HFS-) induced long-Term potentiation (LTP) and forskolin-(FSK-) induced LTP. sEH inhibitor (sEHI) N-[1-(oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU) and exogenous 14,15-EET increased HFS-LTP, which could be blocked by an N-methyl-D-Aspartate (NMDA) receptor subunit NR2B antagonist. TPPU-or 14,15-EET-facilitated FSK-mediated LTP can be potentiated by an A1 adenosine receptor antagonist and a phosphodiesterase inhibitor, but is prevented by a cAMP-dependent protein kinase (PKA) inhibitor. sEHI and 14,15-EET upregulated the activation of extracellular signal-regulated kinases (ERKs) and Ca2+/calmodulin-(CaM-) dependent protein kinase II (CaMKII). Phosphorylation of synaptic receptors NR2B and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 was increased by TPPU and 14,15-EET administration. These results indicated that EETs increased NMDAR-and FSK-mediated synaptic potentiation via the AC-cAMP-PKA signaling cascade and upregulated the ERKs and CaMKII, resulting in increased phosphorylation of NR2B and GluR1 in the hippocampus.

UR - http://www.scopus.com/inward/record.url?scp=85029174657&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029174657&partnerID=8YFLogxK

U2 - 10.1155/2017/3467805

DO - 10.1155/2017/3467805

M3 - Article

VL - 2017

JO - Neural Plasticity

JF - Neural Plasticity

SN - 2090-5904

M1 - 3467805

ER -