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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 H2O2, 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.
| Abbreviations | ||
| DHEA | = | dehydroepiandrosterone |
| G6PD | = | glucose-6-phosphate dehydrogenase |
| PPP | = | pentose phosphate pathway |
| R5P | = | ribose-5-phosphate |
| DMSO | = | dimethyl sulfoxide |
| NADPH | = | reduced form of nicotinamide adenine dinucleotide phosphate |
| ROS | = | reactive oxygen species |
| = | superoxide | |
| PMA | = | phorbol myristate acetate |
| 8-oxo-dG | = | 8-oxo-deoxyguanosine |
| GSH/GSSG | = | reduced glutathione/oxidized glutathione |
| SOD | = | superoxide dismutase |
| MPO | = | myeloperoxidase |
| D-PBS (−) | = | Dulbecco's phosphate buffered saline (free of Ca and Mg ions) |
| GPx | = | glutathione peroxidase |
| GR | = | glutathione reductase |
| dG | = | deoxyguanosine |
| FAS | = | fatty acid synthase |
| ACC1 | = | acetyl-CoA carboxylase 1 |
| HBSS-HEPES | = | Hanks’ balanced salt solution containing 30 mM HEPES |
| X5P | = | xylulose-5-phosphate |
| ChREBP | = | carbohydrate-responsive element binding protein |
| Abbreviations | ||
| DHEA | = | dehydroepiandrosterone |
| G6PD | = | glucose-6-phosphate dehydrogenase |
| PPP | = | pentose phosphate pathway |
| R5P | = | ribose-5-phosphate |
| DMSO | = | dimethyl sulfoxide |
| NADPH | = | reduced form of nicotinamide adenine dinucleotide phosphate |
| ROS | = | reactive oxygen species |
| = | superoxide | |
| PMA | = | phorbol myristate acetate |
| 8-oxo-dG | = | 8-oxo-deoxyguanosine |
| GSH/GSSG | = | reduced glutathione/oxidized glutathione |
| SOD | = | superoxide dismutase |
| MPO | = | myeloperoxidase |
| D-PBS (−) | = | Dulbecco's phosphate buffered saline (free of Ca and Mg ions) |
| GPx | = | glutathione peroxidase |
| GR | = | glutathione reductase |
| dG | = | deoxyguanosine |
| FAS | = | fatty acid synthase |
| ACC1 | = | acetyl-CoA carboxylase 1 |
| HBSS-HEPES | = | Hanks’ balanced salt solution containing 30 mM HEPES |
| X5P | = | xylulose-5-phosphate |
| ChREBP | = | carbohydrate-responsive element binding protein |