Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells
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- Li Bing
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Baba Takashi
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Miyabayashi Kanako
- Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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- Sato Tetsuya
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
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- Shima Yuichi
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan Department of Anatomy, Kawasaki Medical School, Kurashiki 701-0192, Japan
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- Ichinose Tomomi
- Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan
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- Miura Daisuke
- Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan
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- Ohkawa Yasuyuki
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
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- Suyama Mikita
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
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- Morohashi Ken-ichirou
- Division of Systems Life Sciences, Graduate School of Systems Life Sciences, Kyushu University, Fukuoka 812-8582, Japan Department of Molecular Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
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Description
Ad4-binding protein/steroidogenic factor 1 (Ad4BP/SF-1), a member of the nuclear receptor superfamily, is expressed in steroidogenic cells and regulates all steroidogenic gene expression. We recently employed mRNA and chromatin immunoprecipitation sequence (ChIP-seq) to demonstrate that Ad4BP/SF-1 directly regulates the expression of nearly all glycolytic genes. The pentose phosphate pathway (PPP) contributes to the production of nicotinamide adenine dinucleotide phosphate (NADPH). Although the expression of PPP genes and intracellular NADPH were decreased by Ad4BP/SF-1 knockdown, these genes were not the direct targets of Ad4BP/SF-1. This study therefore investigates whether Ad4BP/SF-1 directly regulates genes implicated in NADPH production. Examination of previously published data sets of mRNA sequence (mRNA-seq) and ChIP-seq strongly suggested a possibility that other NADPH-producing genes, such as malic enzyme 1 (Me1) and methylenetetrahydrofolate dehydrogenase 2 (Mthfd2), are the direct targets of Ad4BP/SF-1. Reporter gene assays and determination of intracellular NADPH concentration supported the notion that Ad4BP/SF-1 regulates NADPH production by regulating these genes. NADPH is required for macromolecule synthesis of compounds such as steroids, and for detoxification of reactive oxygen species. When synthesizing steroid hormones, steroidogenic cells consume NADPH through enzymatic reactions mediated by steroidogenic P450s. NADPH is also consumed through elimination of reactive oxygen species produced as the byproducts of the P450 reactions. Overall, Ad4BP/SF-1 potentially maintains the intracellular NADPH level through cooperative regulation of genes involved in the biological processes for consumption and supply.
Journal
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- Endocrine Journal
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Endocrine Journal 64 (3), 315-324, 2017
The Japan Endocrine Society