A genome-wide expression analysis to study the effects of thyroid-disrupting chmicals on the expression of the hormone responsive genes

• Project/Area Number: 20710051
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Shizuoka University
• Principal Investigator: ISHIHARA Akinori 静岡大学, 理学部, 講師 (70432193)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 内分泌かく乱物質 / 分子生物学 / バイオインフォマティクス

Research Abstract

Hydroxylated polychlorinated are suspected to disrupt post-embryonic neural development in the brains of mammals including humans. Because thyroid hormones play a role in the perinatal development of the central nervous system, the thyroid system is thought to be one of the important endpoints affected by several endocrine-disrupting chemicals including PCBs. We studied the effects of these compounds on thyroid hormone function in the brain by using metamorphosing tadpoles of the African clawed toad as a model for mammalian post-embryonic development. The metamorphosis assay revealed that these compounds inhibit thyroid hormone-induced metamorphosis. Genome-wide gene expression analysis in the brain following short-term exposure demonstrated that delayed metamorphosis could partially be caused by disruption of thyroid hormone-induced gene expression.

Research Products

• [Journal Article] RNA polymerase II phospho rylation at serine 2 and histone H3 tri-methylation at lysine 36 are key steps for thyroid hormone receptorβgene activation by thyroid hormone in Rana catesbeiana tadpole liver (2012)
  • Author(s): Mochizuki K, Ishihara A, Goda T, Yamauchi K.
  • Journal Title: Biochem Biophys Res Commun Volume: 417(3) Pages: 1069-73
  • Peer Reviewed
• [Journal Article] RNA polymerase II phosphorylation at serine 2 and histone H3 tri-methylation at,lysine 36 are key steps for thyroid hormone receptor β gene activation by thyroid hormone in Rana catesbeiana tadpole liver (2012)
  • Author(s): Mochizuki K, Ishihara A, Goda T, Yamauchi K
  • Journal Title: Biochem Biophys Res Commun Volume: 417 Issue: 3 Pages: 1069-1073
  • DOI: 10.1016/j.bbrc.2011.12.097
  • Peer Reviewed
• [Journal Article] Gene expression profilig to examine the thyroid hormone-disrupting activity of hydroxyl Ted polychlorinaed biphenyls in metamo rphosing amphibian tadpole (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K
  • Journal Title: J Biochem Mol Toxicol Volume: 25(5) Pages: 303-11
  • Peer Reviewed
• [Journal Article] Gene expression profiling to examine the thyroid hormone-disrupting activity of hydroxylated polychlorinated biphenyls in metamorphosing amphibian tadpole (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K
  • Journal Title: J Biochem Mol Toxicol Volume: 25 Issue: 5 Pages: 303-311
  • DOI: 10.1002/jbt.20390
  • Peer Reviewed
• [Journal Article] Gene expression profiling to examine the thyroid hormone-disrupting activity of hydroxylated polychlorinated biphenyls in metamorphosing amphibian tadpole. (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K.
  • Journal Title: J Biochem Mol Toxicol in press
  • Peer Reviewed
• [Journal Article] Gene expression profiling to examine the thyroid hormone-disrupting activity of hydroxylated polychlorinated biphenyls in metamorphosing amphibian tadpole. (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K.
  • Journal Title: J Biochem Mol Toxicol.
  • Peer Reviewed
• [Journal Article] Time of Day and Nutrients in Feeding Govern Daily Expression Rhythms of the Gene for Sterol Regulatory Element-binding Protein(SREBP)-1 in the Mouse Liver (2010)
  • Author(s): Matsumoto E, Ishihara A, Tamai S, Nemoto A, Iwase K, Hiwasa T, Shibata S, Takiguchi M
  • Journal Title: J Biol Chem Volume: 285(43) Pages: 33028-36
  • Peer Reviewed
• [Journal Article] Time of Day and Nutrients in Feeding Govern Daily Expression Rhythms of the Gene for Sterol Regulatory Element-binding Protein (SREBP)-1 in the Mouse Liver (2010)
  • Author(s): Matsumoto E, Ishihara A, Tamai S, Nemoto A, Iwase K, Hiwasa T, Shibata S, Takiguchi M.
  • Journal Title: J Biol Chem 285(43) Pages: 33028-33036
  • Peer Reviewed
• [Journal Article] Time of day and nutrients in feeding govern daily expression rhythms of the gene for sterol regulatory element-binding protein (SREBP)-1 in the mouse liver. (2010)
  • Author(s): Matsumoto E, Ishihara A, Tamai S, Nemoto A, Iwase K, Hiwasa T, Shibata S, Takiguchi M.
  • Journal Title: J Biol Chem. Volume: 285 Pages: 33028-33036
  • Peer Reviewed
• [Journal Article] Evolutionary changes to trans thyretin : de velo pmentally regulate and tissue-specific gene expression (2009)
  • Author(s): Yamauchi K, Ishihara A
  • Journal Title: FEBS J Volume: 276(19) Pages: 5357-66
  • Peer Reviewed
• [Journal Article] In vitro thyroid hormone-disrupting activity in effluents and surface waters in Thailand (2009)
  • Author(s): Ishihara A, Rahman FB, Leelawatwattana L, Prapunpoj P, Yamauchi K
  • Journal Title: Environ Toxicol Chem Volume: 28(3) Pages: 586-94
  • Peer Reviewed
• [Journal Article] Evolutionary changes to transthyretin : developmentally regulated and tissue-specific gene expression. (2009)
  • Author(s): Yamauchi K, Ishihara A.
  • Journal Title: FEBS J. 276(19) Pages: 5357-5366
  • Peer Reviewed
• [Journal Article] In vitro thyroid hormone-disrupting activity in effluents and surface waters in Thailand. (2009)
  • Author(s): Ishihara A, Rahman FB, Leelawatwattana L, Prapunpoj P, Yamauchi K.
  • Journal Title: Environ Toxicol Chem. 28(3) Pages: 586-594
  • Peer Reviewed
• [Journal Article] Evolutionary changes to transthyretin : developmentally regulated and tissue-specific gene expression (2009)
  • Author(s): Yamauchi K, Ishihara A
  • Journal Title: FEBS J. 276 Pages: 5357-5366
  • Peer Reviewed
• [Journal Article] IN VITRO THYROID HORMONE-DISRUPTING ACTIVITY IN EFFLUENTS AND SURFACE WATERS IN THAILAND (2009)
  • Author(s): Ishihara A, Rahman FB, Loelawatwa Ltana L, Prapunpoj P, Yamauchi K
  • Journal Title: Environ Toxicol Chem 20 Pages: 586-594
  • Peer Reviewed
• [Journal Article] Interaction of diethylstilbestrol and ioxynil with trans thyretin in chicke serum (2008)
  • Author(s): Eguchi R, Ishihara A, Yamauchi K
  • Journal Title: Comp Biochem Physiol C Toxicol Pharmacology Volume: 147(3) Pages: 345-50
  • Peer Reviewed
• [Journal Article] Interaction of diethylstilbestrol and ioxynil with transthyretin in chicken serum. (2008)
  • Author(s): Eguchi R, Ishihara A, Yamauchi K.
  • Journal Title: Comp Biochem Physiol C Toxicol Pharmacol. 147(3) Pages: 345-350
  • Peer Reviewed
• [Presentation] The Availability of Genome-wide Expression Analysis as a Powerful Tool to Detect the Effects of Environmental Chemicals on Thyroid System (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K
  • Organizer: Shizuoka University International Symposium
  • Place of Presentation: 静岡(B-nest)
  • Year and Date: 2011-11-29
• [Presentation] Modulation of the Effect of Phenolic Compounds by Their Interaction with Serum Protein (2011)
  • Author(s): Akiyoshi S, Sai G, Ishihara A, Yamauchi K
  • Organizer: Shizuoka University International Symposium
  • Place of Presentation: 静岡(B-nest)
  • Year and Date: 2011-11-28
• [Presentation] he Effects of Hydroxylated Polychlorinated Biphenyls on the Expression of Thyroid Hormone Response Genes (2011)
  • Author(s): Makita Y, Ishihara A, Yamauchi K
  • Organizer: Shizuoka University International Symposium
  • Place of Presentation: 静岡(B-nest)
  • Year and Date: 2011-11-28
• [Presentation] The Availability of Genome-wide Expression Analysis as a Powerful Tool to Detect the Effects of Environmental Chemicals on Thyroid System (2011)
  • Author(s): Akinori Ishihara, Yu Makita, and Kiyoshi Yamauchi
  • Organizer: Shizuoka University International Symposium 2011?Initiatives for Crossing Boundaries within Science and Technology
  • Place of Presentation: Shizuoka, Japan
• [Presentation] Modulation of the Effect of Phenolic Compounds by Their Interaction with Serum Protein (2011)
  • Author(s): Sakura Akiyoshi, Gobun Sai, Akinori Ishihara, and Kiyoshi Yamauch
  • Organizer: Shizuoka University International Symposium 2011?Initiatives for Crossing Boundaries within Science and Technology
  • Place of Presentation: Shizuoka, Japan
• [Presentation] The Effects of Hydroxylated Polychlorinated Biphenyls on the Expression of Thyroid Hormone Response Genes (2011)
  • Author(s): Yu Makita, Akinori Ishihara, and Kiyoshi Yamauchi
  • Organizer: Shizuoka University International Symposium 2011?Initiatives for Crossing Boundaries within Science and Technology
  • Place of Presentation: Shizuoka, Japan
• [Presentation] A genome-wide expression analysis revealed the effects of hydroxylated polychlorinated biphenyls on the thyroid hormone function in metamorphosing African clawed toad Xenopus laevis (2011)
  • Author(s): Akinori Ishihara, Yu Makita, and Kiyoshi Yamauchi
  • Organizer: ICCPB2011
  • Place of Presentation: Nagoya, Japan
• [Presentation] Modulation of the extracellular distribution (2011)
  • Author(s): Kiyoshi Yamauchi, Gobun Sai, Sakura Akiyoshi, and Akinori Ishihara
  • Organizer: ICCPB2011
  • Place of Presentation: Nagoya, Japan
• [Presentation] A genome-wide expression analysis revealed the effects of hydroxylated polychlorinated biphenyls on the thyroid hormone function in metamorp hosing African clawed toad Xenopus laevis (2011)
  • Author(s): Ishihara A, Makita Y, Yamauchi K
  • Organizer: ICCPB2011
  • Place of Presentation: 名古屋(名古屋国際会議場)
• [Presentation] Modulation of the extracellular distribution, cellular uptake, and cellular action of phenolic compounds with thyroid hormone disrupting activity by serum proteins (2011)
  • Author(s): Yamauchi K, Sai G, Akiyoshi S, Ishihaia A
  • Organizer: ICCPB2011
  • Place of Presentation: 名古屋(名古屋国際会議場)
• [Presentation] 網羅的遺伝子発現解析による化学物質応答メカニズムの検討 (2010)
  • Author(s): 石原顕紀、蒔田優、山内清志
  • Organizer: 日本比較内分泌学会
  • Place of Presentation: グランシップ(静岡県)
  • Year and Date: 2010-11-19
• [Presentation] 血清蛋白質は種特異的に化学物質の甲状腺ホルモン撹乱作用を抑制する (2010)
  • Author(s): 山内清志、秋吉さくら、崔語旻、石原顕紀
  • Organizer: 日本比較内分泌学会
  • Place of Presentation: グランシップ(静岡県)
  • Year and Date: 2010-11-19
• [Presentation] 変態期アフリカツメガエル脳における甲状腺ホルモン作用に及ぼす水酸化PCBの影響 (2010)
  • Author(s): 蒔田優、石原顕紀、山内清志
  • Organizer: 日本動物学会
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2010-09-25
• [Presentation] 甲状腺系撹乱化学物質と血清タンパク質の相互作用 (2010)
  • Author(s): 秋吉さくら、江口良二、石原顕紀、山内清志
  • Organizer: 日本動物学会
  • Place of Presentation: 東京大学(東京都)
  • Year and Date: 2010-09-25
• [Presentation] 網羅的遺伝子発現解析による化学物質応答メカニズムの検討 (2010)
  • Author(s): 石原顕紀,蒔田優,山内清志
  • Organizer: 日本比較内分泌学会第35回大会
  • Place of Presentation: 静岡
• [Presentation] 血清蛋白質は種特異的に化学物質の甲状腺ホルモン撹乱作用を抑制す (2010)
  • Author(s): 山内清志,秋吉さくら,崔語旻,石原顕紀
  • Organizer: 日本比較内分泌学会第35回大会
  • Place of Presentation: 静岡
• [Presentation] 変態期アフリカツメガエル脳における甲状腺ホルモン作用に及ぼす水酸化PCBの影響 (2010)
  • Author(s): 蒔田優,石原顕紀,山内清志
  • Organizer: 日本動物学会第81回大会
  • Place of Presentation: 東京
• [Presentation] 甲状腺系撹乱化学物質と血清タンパク質の相互作用 (2010)
  • Author(s): 秋吉さくら,江口良二,石原顕紀,山内清志
  • Organizer: 日本動物学会第81回大会
  • Place of Presentation: 東京
• [Presentation] 血清蛋白質は種特異的に化学物質の甲状腺ホルモン撹乱作用を抑制する (2010)
  • Author(s): 山内清志, 秋吉さくら, 崔語旻, 石原顕紀
  • Organizer: 日本比較内分泌学会第35回大会
  • Place of Presentation: 静岡
• [Presentation] タイ王国環境水中に含まれる甲状腺撹乱活性のバイオアッセイによる検出 (2008)
  • Author(s): 石原顕紀、ラハマンファルハナ、山内清志
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡大学七隈キャンパス
  • Year and Date: 2008-09-07
• [Presentation] タイ王国環境水中に含まれる甲状腺撹乱活性のバイオアッセイによる (2008)
  • Author(s): 石原顕紀、ラハマンファルハナ、山内清志
  • Organizer: 検出日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Presentation] タイ王国環境水中に含まれる甲状腺撹乱活性のバイオアッセイによる検出 (2008)
  • Author(s): 石原顕紀、ラハマン ファルハナ、山内清志
  • Organizer: 日本動物学会第79回大会
  • Place of Presentation: 福岡
• [Book] TTR and Endocrine Disruptors. In : Recent Advances in Transthyretin Evolution, Structure and Biological Functions (2009)
  • Author(s): Yamauchi, K., Ishihara, A.
  • Publisher: Springer
• [Book] Structure and Biological Functions.
  • Author(s): Yamauchi, K., Ishihara, A.
  • Publisher: TTR and Endocrine Disruptors. In : Recent Advances in Transthyretin Evolution
• [Remarks]
  • URL: http://www.ipc.shizuoka.ac.jp/.sbkyama/
• [Remarks]
  • URL: http://www.ipc.shizuoka.ac.jp/sbkyama/