title: Epigallocatechin 3-gallate attenuates neuronal damage induced by 3-hydroxykynurenine.
abstract: 3-Hydroxykynurenine (3-HK), which is an endogenous metabolite of tryptophan in the kynurenine pathway, is a potential neurotoxin in several neurodegenerative disorders. Epigallocatechin 3-gallate (EGCG), a major compound of green tea, is recognized as a promising natural substance for protection against neuronal diseases. This study investigated the possible protective roles and mechanism of EGCG, against 3-HK-induced cell death. It was found that 3-HK induces neuronal cell death in the human neuroblastoma SH-SY5Y cell line. The reduced cell viability produced characteristic features such as cell shrinkages, plasma membrane blebbing, chromatin condensation, and nuclear fragmentation. The cells treated with 3-HK showed an increase in the concentration of reactive oxygen species (ROS) as well as in caspase activity. In addition, both are involved in the 3-HK-induced apoptosis. EGCG attenuated the cell viability reduction by 3-HK in both a dose- and time-dependent manner. Optical microscopy showed that EGCG inhibited the cell morphological features in the 3-HK-treated cells. Furthermore, the increase in the ROS concentration and the caspase activities by 3-HK were also attenuated by EGCG. These results showed that EGCG has a protective effect on the 3-HK induced cell death by inhibiting ROS production and caspase activity. The results suggest that EGCG might be a promising protective substance against the neuronal degenerative diseases.
authors.affiliation: Department of Pathology, Medical School, Chung Ang University, 221 Heuksuk-Dong, Dongjak-Gu, Seoul 156-756, South Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Hyung Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Tae Jin
authors.initials: TJ
authors.lastname: Lee
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Eon Sub
authors.initials: ES
authors.lastname: Park
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Choi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000633:toxicity*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C005045:3-hydroxykynurenine; D007737:Kynurenine; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases