Neuroprotection by (-)-epigallocatechin-3-gallate in a rat model of stroke is mediated through inhibition of endoplasmic reticulum stress.

Abstract

(-)-Epigallocatechin-3‑gallate (EGCG), the predominant constituent of green tea, has been demonstrated to be neuroprotective against stroke in rats. However, the precise mechanism of EGCG responsible for neuroprotective activity remains unclear and no established treatment for decreasing the resulting neurological damage of stroke exists. The present study was designed to investigate the neuroprotective mechanism of EGCG on transient focal cerebral ischemia in rats. EGCG, when applied immediately following ischemia, significantly decreased the expression of endoplasmic reticulum stress (ERS)‑related markers, [glucose‑regulated protein 78 (GRP78), C/EBP‑homologous protein (CHOP) and caspase‑12] and apoptosis 24 h following reperfusion. EGCG treatment also significantly reduced infarct volumes and increased neurological scores which was correlated with elevated levels of TRPC6 and phosphorylation of cAMP/Ca2+ response element‑binding protein (p‑CREB) activity, and decreased calpain‑specific aII‑spectrin breakdown product (SBDP145) activity. When mitogen‑activated protein kinase kinase (MEK) activity was specifically inhibited, the neuroprotective effect of EGCG was attenuated and a correlated decrease in CREB activity was observed. In conclusion, the results clearly demonstrated that intracerebroventricular injection of EGCG immediately following ischemia, inhibits ERS and improves the neurological status of rats that have undergone middle cerebral artery occlusion via the inhibition of calpain‑mediated TRPC6 proteolysis and the subsequent activation of CREB via the MEK/extracellular signal-regulated kinases (ERK) pathway.

• Authors: Chengye Yao, Jiancheng Zhang, Gongping Liu, Fang Chen, Yun Lin
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 9 Issue 1 Pg. 69-76 (Jan 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 24193141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic AMP Response Element-Binding Protein
• Ddit3 protein, rat
• Flavonoids
• GRP78 protein, rat
• Heat-Shock Proteins
• Neuroprotective Agents
• TRPC Cation Channels
• Trpc6 protein, rat
• Spectrin
• Transcription Factor CHOP
• Catechin
• epigallocatechin gallate
• Mitogen-Activated Protein Kinase Kinases
• Caspase 12
• 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 12 (metabolism)
• Catechin (analogs & derivatives, pharmacology, therapeutic use)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Disease Models, Animal
• Endoplasmic Reticulum Stress (drug effects)
• Flavonoids (pharmacology, therapeutic use)
• Heat-Shock Proteins (metabolism)
• Male
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Spectrin (metabolism)
• Stroke (drug therapy)
• TRPC Cation Channels (antagonists & inhibitors, metabolism)
• Transcription Factor CHOP (metabolism)