Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Free Radic Res. 2009 Oct;43(10):922-31. doi: 10.1080/10715760903137093. Epub 2009 Aug 12.
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.
脱氢表雄酮(DHEA)是葡萄糖-6-磷酸脱氢酶(G6PD)的可逆抑制剂,作为一种抗氧化和抗衰老补充剂,其应用日益广泛。本研究探讨了 DHEA 对人早幼粒细胞白血病细胞系 HL60 向中性粒细胞样细胞分化过程中 G6PD 的表达和氧化应激状态的影响。本研究用二甲基亚砜(DMSO)诱导 HL60 分化(DMSO-HL60/DHEA)或不诱导(DMSO-HL60)DHEA。在分化过程中,G6PD 的活性、mRNA 和蛋白水平均增加。DHEA 进一步增加了这些水平。DHEA 本身抑制了 PMA 刺激的 DMSO-HL60 中超氧化物的产生。然而,在没有 DHEA 的情况下,用 PMA 刺激的 DMSO-HL60/DHEA 产生的超氧化物和 8-氧-脱氧鸟苷比 PMA 刺激的 DMSO-HL60 更多。加入 H(2)O(2)后,DMSO-HL60/DHEA 中的还原型谷胱甘肽与氧化型谷胱甘肽的比值低于 DMSO-HL60。这些发现表明,DHEA 既具有抗氧化作用,也具有促氧化作用。