title: Dehydroepiandrosterone increased oxidative stress in a human cell line during differentiation.
abstract: Dehydroepiandrosterone (DHEA), a reversible inhibitor of glucose-6-phosphate dehydrogenase (G6PD), is increasingly taken as an antioxidative and anti-ageing supplement. This study investigated the effects of DHEA on the expression of G6PD and on the state of oxidative stress in a human promyelocytic leukaemia cell line, HL60, during the differentiation to neutrophil-like cell. This study differentiated HL60 with dimethyl sulfoxide (DMSO) in the presence (DMSO-HL60/DHEA) or absence (DMSO-HL60) of DHEA. During the differentiation, activity, mRNA and protein levels of G6PD were increased. DHEA increased these levels further. DHEA by itself suppressed the production of superoxide from DMSO-HL60 upon stimulation with phorbol myristate acetate (PMA). However, DMSO-HL60/DHEA stimulated with PMA in the absence of DHEA produced superoxide and 8-oxo-deoxyguanosine more than PMA-stimulated DMSO-HL60. After addition of H(2)O(2), the ratio of reduced glutathione to oxidized glutathione was lower in DMSO-HL60/DHEA than in DMSO-HL60. These findings indicate that DHEA acts both as an antioxidant and as a pro-oxidant.
authors.affiliation: Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Izumo
authors.forename: Masahisa
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Komatsu
authors.forename: Kohji
authors.initials: K
authors.lastname: Aoyama
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Bandow
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsuguchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Toru
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003687:Dehydroepiandrosterone; D005954:Glucosephosphate Dehydrogenase; D019255:NADPH Oxidases; D004121:Dimethyl Sulfoxide