title: Role of reactive oxygen species in apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells.
abstract: We have previously reported that N-ethylmaleimide induces apoptosis through activation of K(+), Cl(-)-cotransport in HepG2 human hepatoblastoma cells. In this study, we investigated the role for reactive oxygen species as a mediator of the apoptosis induced by N-ethylmaleimide. N-ethylmaleimide induced a significant elevation of intracellular level of reactive oxygen species. Treatment with antioxidants (N-acetyl cysteine, N,N'-diphenyl-p-phenylenediamine) which markedly suppressed generation of reactive oxygen species, significantly inhibited the N-ethylmaleimide-induced activation of K(+), Cl(-)-cotransport and apoptosis. Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide. These results suggest that reactive oxygen species generated through activation of NADPH oxidase may play a role in the N-ethylmaleimide-induced stimulation of K(+), Cl(-)-cotransport and apoptosis in HepG2 cells.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyongsan 712-749, South Korea.
authors.forename: J A
authors.initials: JA
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kang
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: H W
authors.initials: HW
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Cho
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002712:Chlorides / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology*; D018197:Hepatoblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D019255:NADPH Oxidases / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species; D027981:Symporters / Q000502:physiology; D000096922:K Cl- Cotransporters
chemical_list: D002712:Chlorides; D005033:Ethylmaleimide; D019255:NADPH Oxidases; D011188:Potassium; D017382:Reactive Oxygen Species; D027981:Symporters; D000096922:K Cl- Cotransporters