(-)-Epigallocatechin gallate, the most active polyphenolic catechin in green tea, presynaptically facilitates Ca2+-dependent glutamate release via activation of protein kinase C in rat cerebral cortex

Chien Wen Chou, Wei Jan Huang, Lu Tai Tien, Su Jane Wang

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26 Citations (Scopus)

Abstract

(-)-epigallocatechin gallate (EGCG), the main polyphenols constituent of green tea, has been reported to improve cognitive decline. Considering the central glutamatergic activity is crucial to cognitive function, the objective of this study was to investigate the effect of EGCG on the release of endogenous glutamate using nerve terminals purified from rat cerebral cortex. Results showed that the release of glutamate evoked by 4-aminopyridine (4AP) was facilitated by EGCG in a concentration-dependent manner, and this effect resulted from an enhancement of vesicular exocytosis and not from an increase in Ca2+-independent efflux via glutamate transporter. Examination of the effect of EGCG on cytoplasmic free Ca2+ concentration ([Ca 2+]c) revealed that the facilitation of glutamate release could be attributed to an increase in Ca2+ influx through N- and P/Q-type voltage-dependent Ca2+ channels. Consistent with this, the EGCG-mediated facilitation of 4AP-evoked glutamate release was significantly prevented in synaptosomes pretreated with a combination of the N-and P/Q-type Ca2+ channel blockers. Additionally, inhibition of protein kinase C (PKC) by treatment with Ro318220 significantly reduced the facilitatory effect of EGCG on 4AP-evoked glutamate release and phosphorylation of PKC or its presynapic target myristoylated alanine-rich C kinase substrate (MARCKS). These results suggest that EGCG effects a facilitation of glutamate release from glutamatergic terminals by positively modulating N- and P/Q-type Ca2+ channel activation through a signaling cascade involving PKC. In this EGCG/PKC signaling cascade facilitating glutamate release, the regulation of cytoskeleton dynamics was also indicated to be involved by disruption of cytoskeleton organization with cytochalasin D occluded the EGCG-mediated facilitation of 4AP-evoked glutamate release.

Original languageEnglish
Pages (from-to)889-902
Number of pages14
JournalSynapse
Volume61
Issue number11
DOIs
Publication statusPublished - Nov 2007
Externally publishedYes

Fingerprint

Catechin
Tea
Cerebral Cortex
Protein Kinase C
Glutamic Acid
4-Aminopyridine
Cytoskeleton
Amino Acid Transport System X-AG
epigallocatechin gallate
Cytochalasin D
Synaptosomes
Exocytosis
Polyphenols
Cognition
Phosphorylation

Keywords

  • Cerebrocortical synaptosomes
  • EGCG
  • Glutamate exocytosis
  • Protein kinase C
  • Voltage-dependent Ca channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology
  • Advanced and Specialised Nursing

Cite this

@article{35862a07111f4bdea29a5b93c900bf81,
title = "(-)-Epigallocatechin gallate, the most active polyphenolic catechin in green tea, presynaptically facilitates Ca2+-dependent glutamate release via activation of protein kinase C in rat cerebral cortex",
abstract = "(-)-epigallocatechin gallate (EGCG), the main polyphenols constituent of green tea, has been reported to improve cognitive decline. Considering the central glutamatergic activity is crucial to cognitive function, the objective of this study was to investigate the effect of EGCG on the release of endogenous glutamate using nerve terminals purified from rat cerebral cortex. Results showed that the release of glutamate evoked by 4-aminopyridine (4AP) was facilitated by EGCG in a concentration-dependent manner, and this effect resulted from an enhancement of vesicular exocytosis and not from an increase in Ca2+-independent efflux via glutamate transporter. Examination of the effect of EGCG on cytoplasmic free Ca2+ concentration ([Ca 2+]c) revealed that the facilitation of glutamate release could be attributed to an increase in Ca2+ influx through N- and P/Q-type voltage-dependent Ca2+ channels. Consistent with this, the EGCG-mediated facilitation of 4AP-evoked glutamate release was significantly prevented in synaptosomes pretreated with a combination of the N-and P/Q-type Ca2+ channel blockers. Additionally, inhibition of protein kinase C (PKC) by treatment with Ro318220 significantly reduced the facilitatory effect of EGCG on 4AP-evoked glutamate release and phosphorylation of PKC or its presynapic target myristoylated alanine-rich C kinase substrate (MARCKS). These results suggest that EGCG effects a facilitation of glutamate release from glutamatergic terminals by positively modulating N- and P/Q-type Ca2+ channel activation through a signaling cascade involving PKC. In this EGCG/PKC signaling cascade facilitating glutamate release, the regulation of cytoskeleton dynamics was also indicated to be involved by disruption of cytoskeleton organization with cytochalasin D occluded the EGCG-mediated facilitation of 4AP-evoked glutamate release.",
keywords = "Cerebrocortical synaptosomes, EGCG, Glutamate exocytosis, Protein kinase C, Voltage-dependent Ca channel",
author = "Chou, {Chien Wen} and Huang, {Wei Jan} and Tien, {Lu Tai} and Wang, {Su Jane}",
year = "2007",
month = "11",
doi = "10.1002/syn.20444",
language = "English",
volume = "61",
pages = "889--902",
journal = "Synapse",
issn = "0887-4476",
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T1 - (-)-Epigallocatechin gallate, the most active polyphenolic catechin in green tea, presynaptically facilitates Ca2+-dependent glutamate release via activation of protein kinase C in rat cerebral cortex

AU - Chou, Chien Wen

AU - Huang, Wei Jan

AU - Tien, Lu Tai

AU - Wang, Su Jane

PY - 2007/11

Y1 - 2007/11

N2 - (-)-epigallocatechin gallate (EGCG), the main polyphenols constituent of green tea, has been reported to improve cognitive decline. Considering the central glutamatergic activity is crucial to cognitive function, the objective of this study was to investigate the effect of EGCG on the release of endogenous glutamate using nerve terminals purified from rat cerebral cortex. Results showed that the release of glutamate evoked by 4-aminopyridine (4AP) was facilitated by EGCG in a concentration-dependent manner, and this effect resulted from an enhancement of vesicular exocytosis and not from an increase in Ca2+-independent efflux via glutamate transporter. Examination of the effect of EGCG on cytoplasmic free Ca2+ concentration ([Ca 2+]c) revealed that the facilitation of glutamate release could be attributed to an increase in Ca2+ influx through N- and P/Q-type voltage-dependent Ca2+ channels. Consistent with this, the EGCG-mediated facilitation of 4AP-evoked glutamate release was significantly prevented in synaptosomes pretreated with a combination of the N-and P/Q-type Ca2+ channel blockers. Additionally, inhibition of protein kinase C (PKC) by treatment with Ro318220 significantly reduced the facilitatory effect of EGCG on 4AP-evoked glutamate release and phosphorylation of PKC or its presynapic target myristoylated alanine-rich C kinase substrate (MARCKS). These results suggest that EGCG effects a facilitation of glutamate release from glutamatergic terminals by positively modulating N- and P/Q-type Ca2+ channel activation through a signaling cascade involving PKC. In this EGCG/PKC signaling cascade facilitating glutamate release, the regulation of cytoskeleton dynamics was also indicated to be involved by disruption of cytoskeleton organization with cytochalasin D occluded the EGCG-mediated facilitation of 4AP-evoked glutamate release.

AB - (-)-epigallocatechin gallate (EGCG), the main polyphenols constituent of green tea, has been reported to improve cognitive decline. Considering the central glutamatergic activity is crucial to cognitive function, the objective of this study was to investigate the effect of EGCG on the release of endogenous glutamate using nerve terminals purified from rat cerebral cortex. Results showed that the release of glutamate evoked by 4-aminopyridine (4AP) was facilitated by EGCG in a concentration-dependent manner, and this effect resulted from an enhancement of vesicular exocytosis and not from an increase in Ca2+-independent efflux via glutamate transporter. Examination of the effect of EGCG on cytoplasmic free Ca2+ concentration ([Ca 2+]c) revealed that the facilitation of glutamate release could be attributed to an increase in Ca2+ influx through N- and P/Q-type voltage-dependent Ca2+ channels. Consistent with this, the EGCG-mediated facilitation of 4AP-evoked glutamate release was significantly prevented in synaptosomes pretreated with a combination of the N-and P/Q-type Ca2+ channel blockers. Additionally, inhibition of protein kinase C (PKC) by treatment with Ro318220 significantly reduced the facilitatory effect of EGCG on 4AP-evoked glutamate release and phosphorylation of PKC or its presynapic target myristoylated alanine-rich C kinase substrate (MARCKS). These results suggest that EGCG effects a facilitation of glutamate release from glutamatergic terminals by positively modulating N- and P/Q-type Ca2+ channel activation through a signaling cascade involving PKC. In this EGCG/PKC signaling cascade facilitating glutamate release, the regulation of cytoskeleton dynamics was also indicated to be involved by disruption of cytoskeleton organization with cytochalasin D occluded the EGCG-mediated facilitation of 4AP-evoked glutamate release.

KW - Cerebrocortical synaptosomes

KW - EGCG

KW - Glutamate exocytosis

KW - Protein kinase C

KW - Voltage-dependent Ca channel

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