Neuroprotective Effect of Gallocatechin Gallate on Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells.

Do Hwi Park,Gwi Seo Hwang,Ki Sung Kang,Jun Yeon Park

doi:10.3390/molecules26051387

Do Hwi Park, Gwi Seo Hwang + Show 2 more

Open Access

https://doi.org/10.3390/molecules26051387

Copy DOI

Abstract

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.

Highlights

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death
The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and the inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) and Jun N-terminal kinases (JNK)
All five catechins were evaluated for their antioxidant activity, and their IC50 values were as follows: GCG (IC50 = 7.29), epigallocatechin gallate (EGCG) (IC50 = 2.52), GC (IC50 = 19.27), ECG (IC50 = 41.4), and EC (IC50 = 52.17); vitamin C (Vit.C) (IC50 = 7.18) was used as a positive control

Summary

Introduction

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. We deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and the inhibition of phosphorylation of ERK and JNK. The antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells. Degenerative brain diseases caused by both genetic and environmental factors, such as oxidative stress, are known causes of neuronal cell death due to neurodegeneration and aging, and studies are being actively pursued to determine their exact cause [1,2,3]. ROS are free radicals produced during oxidative stress and are the leading cause of diseases of the brain and nervous system [4,5]

Objectives

Methods

Results

Conclusion