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(−)‐Epigallocatechin‐3‐Gallate Protects against TNF alpha and Hydrogen Peroxide Induced Apoptosis in a Cell Culture Model of Parkinson's Disease
Author(s) -
Xu Qi,
Kanthasamy Anumantha,
Reddy Manju
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.922.9
Subject(s) - oxidative stress , chemistry , hepcidin , apoptosis , tumor necrosis factor alpha , reactive oxygen species , hydrogen peroxide , viability assay , ferroportin , antioxidant , pharmacology , inflammation , microbiology and biotechnology , endocrinology , biochemistry , medicine , biology
Several factors including oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson's disease (PD). Considering the entwined relationship among these factors, (−)‐Epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its antioxidant, iron chelating and anti‐inflammatory properties. The objective of this study is to determine whether EGCG protects immortalized rat mesencephalic cells from hydrogen peroxide (H 2 O 2 ) and TNF alpha induced apoptosis. We chose 50µM H 2 O 2 and 30ng/ml TNF alpha in experiments based on our preliminary data. Our results show that caspase‐3 activity was increased to 2.8 fold (P<0.001) and 1.5 fold (P<0.01) with H 2 O 2 and TNF alpha treatment; however, EGCG pretreatment significantly decreased the caspase activity by 50% (P<0.001) and 31% (P<0.05). Cell viability was reduced to 69.16% (P<0.01) and 89% (P<0.01) by H 2 O 2 and TNF alpha, which is almost completely blocked by EGCG pretreatment. In addition, 10µM EGCG pretreatment also significantly protected against H 2 O 2 induced reactive oxygen species in a time dependent manner. TNF alpha or ferrous iron up‐regulated hepcidin and down‐regulated ferroportin expression, and EGCG pretreatment reversed this effect, indicating EGCG can normalize iron overload by altering iron influx and efflux mechanisms. Collectively, our results show that EGCG protects against both TNF alpha and H 2 O 2 induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated by iron regulated proteins hepcidin and ferroportin.