Low-dose effects of bisphenol A are induced by tandem binding of nuclear receptors on DNA
Project/Area Number |
25701008
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Partial Multi-year Fund |
Research Field |
Risk sciences of radiation and chemicals
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Research Institution | Kyushu University |
Principal Investigator |
Matsushima Ayami 九州大学, 理学(系)研究科(研究院), 准教授 (60404050)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
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Keywords | 分子認識 / 人体有害物質 / 内分泌撹乱物質 / リスク評価 / タンパク質 / 受容体 / 生理活性物質 / 転写 / 構造活性相関 |
Outline of Final Research Achievements |
An endocrine-disrupting chemical bisphenol A (BPA) induces adverse low-dose effects in reproductive organs and in brains. The molecular mechanisms of low-dose effects are unclear, because the binding of BPA to ERα or ERβ is very weak. We found that the transcription activity of ERα induced by BPA is remarkably reinforced by the co-existence of estrogen-related receptor α (ERRα). We have hypothesized that the ERα dimer binds to estrogen response elements (EREs) on DNA at multiple consecutive sites, which are separated at specific intervals, and induces synergistic activation. We therefore plan to explore the optimized nucleotide spacer length between the hormone response elements for ERα-ERRα synergistic transcriptional function. We found that the greatest ERα-ERRα synergistic transcriptional activation was detected with 11 bp-spacer nucleotides. We also analyzed the ER and ERR mRNA expression levels in several cell lines. Their expression levels were different in each cell.
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Report
(4 results)
Research Products
(123 results)
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[Journal Article] Expression analysis of neuropeptide PDF mRNA in the hypoactive and hyperactive fruit flies Drosophila melanogaster.2016
Author(s)
Tokumaru, A., Matsuo, A., Umeno, S., Matsuyama, Y., Nakamura, M., Sumiyoshi, M., Liu, X., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science 2015
Volume: -
Pages: 317-318
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] SCN Circadian rhythm signal transduction neuropeptides evoke hypoactive phenotype differently in male and female mice.2016
Author(s)
Sugiyama, M., Motomatsu, Y., Matsuyama, Y., Kajiyama, S., Kameda, T., Saito, T., Uchimura, E., Liu, X., Matsushima, A., and Shimohigashi. Y.
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Journal Title
Peptide Science 2015
Volume: -
Pages: 53-54
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Bisphenol A-induced substantial peak decay of Drosophila circadian neuropeptide hugin mRNA expression.2015
Author(s)
Umeno, S., Matsuo, A., Matsuyama, Y., Nakamura, M., Koga, K., Liu, X., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science 2014
Volume: -
Pages: 41-42
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Alternative polyadenylation analyses of neuropeptide genes in bisphenol A-exposed hypoactive mouse brain.2015
Author(s)
Sugiyama, M., Kajiyama, S., Saito, T., Uchimura, E., Motomatsu, Y., Matsuo, A., Matsushima, A., and Shimohigashi. Y.
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Journal Title
Peptide Science 2014
Volume: -
Pages: 345-346
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Bisphenol A-induced substantial peak decay of Drosophila circadian neuropeptide hugin mRNA expression2015
Author(s)
Umeno, S., Matsuo, A., Matsuyama, Y., Nakamura, M., Koga, K., Liu, X., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science 2014
Volume: -
Pages: 41-42
Related Report
Peer Reviewed
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[Journal Article] Alternative polyadenylation analyses of neuropeptide genes in bisphenol A-exposed hypoactive mouse brain2015
Author(s)
Sugiyama, M., Kajiyama, S., Saito, T., Uchimura, E., Motomatsu, Y., Matsuo, A., Matsushima, A., and Shimohigashi. Y.
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Journal Title
Peptide Science 2014
Volume: -
Pages: 345-346
Related Report
Peer Reviewed
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[Journal Article] Specific Role of Phe Residues in Opioid Peptide Met-enkephalin- Arg-Phe in Binding to All Three Opioid Receptors.2014
Author(s)
Motomatsu, Y., Nishimura, H., Matsumoto, Y., Inamine, S., Kuramitsu, Y., Matsushima, A., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 317-318
Related Report
Peer Reviewed
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[Journal Article] Structure-activity Studies on the Halogenated Phe-containing Neuropeptide Substance P Analogs.2014
Author(s)
Kuramitsu, Y., Nishimura, H., Nakamura, R., Suyama, K., Matsushima, A., Nose, T., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 319-320
Related Report
Peer Reviewed
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[Journal Article] Functionally Essential Amino Acid Residues in ORL1 Nociceptin Receptor for Ligand-stimulated Receptor Activation.2014
Author(s)
Nishimura, H., Li, J., Isozaki, K., Abe, Y., Inamine, S., Matsushima, A., Costa, T., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 333-334
Related Report
Peer Reviewed
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[Journal Article] Expression and Mutation Analyses of Brain Neuropeptide Genes of Rndocrine-disrupting Bisphenol A-exposed Hypoactive Mouse.2014
Author(s)
Sugiyama, M., Matsuo, A., Saito, T., Uchimura, E., Liu, X., Matsushima, A., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 453-454
Related Report
Peer Reviewed
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[Journal Article] Influence Analysis of the Circadian Evening Pacemaker Neuropeptide hugγ Gene in the Bisphenol A-exposed Fruit Fly Drosophila Brain.2014
Author(s)
Umeno, S., Matsuo, A. , Matsuyama, Y., Nakamura, M., Takeda, Y., Sumiyoshi, M., Liu, X., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 455-456
Related Report
Peer Reviewed
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[Journal Article] Bisphenol A-induced Epigenetic Mutations in Circadian Pacemaker Neuropeptide mRNAs of Hyperactive Drosophila Fruit Flies.2014
Author(s)
Matsuo, A., Umeno, S., Matsuyama, Y., Nakamura, M., Takeda, Y., Sumiyoshi, M., Liu, X., Matsushima, A., Shimohigashi, M., and Shimohigashi, Y.
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Journal Title
Peptide Science
Volume: 2013
Pages: 457-458
Related Report
Peer Reviewed
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