Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells

Bing Li, Takashi Baba, Kanako Miyabayashi, Tetsuya Sato, Yuichi Shima, Tomomi Ichinose, Daisuke Miura, Yasuyuki Ohkawa, Mikita Suyama, Ken Ichirou Morohashi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)315-324
Number of pages10
JournalEndocrine Journal
Volume64
Issue number3
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Steroidogenic Factor 1
NADP
Genes
Pentose Phosphate Pathway
Chromatin Immunoprecipitation
malate dehydrogenase (decarboxylating)
Methylenetetrahydrofolate Dehydrogenase (NADP)
Reactive Oxygen Species
Steroids
Gene Knockdown Techniques
Biological Phenomena
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells. / Li, Bing; Baba, Takashi; Miyabayashi, Kanako; Sato, Tetsuya; Shima, Yuichi; Ichinose, Tomomi; Miura, Daisuke; Ohkawa, Yasuyuki; Suyama, Mikita; Morohashi, Ken Ichirou.

In: Endocrine Journal, Vol. 64, No. 3, 01.01.2017, p. 315-324.

Research output: Contribution to journalArticle

Li, Bing ; Baba, Takashi ; Miyabayashi, Kanako ; Sato, Tetsuya ; Shima, Yuichi ; Ichinose, Tomomi ; Miura, Daisuke ; Ohkawa, Yasuyuki ; Suyama, Mikita ; Morohashi, Ken Ichirou. / Role of Ad4-binding protein/steroidogenic factor 1 in regulating NADPH production in adrenocortical Y-1 cells. In: Endocrine Journal. 2017 ; Vol. 64, No. 3. pp. 315-324.
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AU - Sato, Tetsuya

AU - Shima, Yuichi

AU - Ichinose, Tomomi

AU - Miura, Daisuke

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AU - Suyama, Mikita

AU - Morohashi, Ken Ichirou

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AB - 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.

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