Dehydroepiandrosterone increased oxidative stress in a human cell line during differentiation.
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.
Izumo
Kimiko
K
Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Horiuchi
Masahisa
M
Komatsu
Masaharu
M
Aoyama
Kohji
K
Bandow
Kenjiro
K
Matsuguchi
Tetsuya
T
Takeuchi
Minoru
M
Takeuchi
Toru
T
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
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D003687:Dehydroepiandrosterone; D005954:Glucosephosphate Dehydrogenase; D019255:NADPH Oxidases; D004121:Dimethyl Sulfoxide