PubMed 24193141

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPC , TRPC6

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

Authors: Chengye Yao, Jiancheng Zhang, Gongping Liu, Fang Chen, Yun Lin

Journal, date & volume: Mol Med Rep, 2014 Jan , 9, 69-76

PubMed link:

(-)-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.