• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

REGULATION OF THYROID FUNCTION BY TRANSCRIPTION FACTOR NF-kappaB

Research Project

Project/Area Number 07457222
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionNagoya University

Principal Investigator

SEO Hisao  Nagoya Univ. Res. Inst. Environ. Med. Professor, 環境医学研究所, 教授 (40135380)

Co-Investigator(Kenkyū-buntansha) IMAI Tsuneo  Nagoya Univ. School of Med. Research Associate, 医学部, 助手 (80252245)
NAGAYA Takashi  Nagoya Univ. Res. Inst. Environ. Med. Research Associate, 環境医学研究所, 助手 (80262913)
KAMBE Fukushi  Nagoya Univ. Res. Inst. Environ. Med. Research Associate, 環境医学研究所, 助手 (00211871)
MURATA Yoshiharu  Nagoya Univ. Res. Inst. Environ. Med. Associate Professor, 環境医学研究所, 助教授 (80174308)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1996: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1995: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsNuclear factor kappa B (NFkB) / Thyroid Cancer / Superoxide Dismutase / Glutathione Peroxidase / Thyrotropin (TSH) / Tumor Necrosis Factor (YNF) / NFκB(Nuclear factor kappa B) / 腫瘍壊死因子(Tumor necrotic factor=TNF) / TSH / NF-κB / FRTL-5細胞 / Mn-SOD / ゲルシフト
Research Abstract

1. ROLE OF ROI-SCAVENGING SYSTEM IN THYROID CANCER
It has been shown that monocytes infiltrating cancer cells secret cytokines with cytocidal effect. The effect of cytokine is exerted by the production of reactive oxygen intermediates (ROI). It is thus possible that ROI-scavenging system in the cancer cell confer the ability to antagonize the cytotoxic effect of the cytokines. In this study, we investigated the expression of mRNAs coding for ROI-scavengers such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and correlated their expression with indices for malignancies such as lymphatic metastasis. It was revealed that the expression of manganese-SOD mRNA was significantly higher in papillary thyroid cancer cells with lymphatic metastasis. There was no correlation with the expression of Copper-Zinc SOD and GPX with lymphatic metastasis. No correlation was found with local invasion and the expression of these mRNAs. It is thus suggested that the higher expression of manganese … More -SOD in papillary cancer cells renders them to survive after lymphatic metastasis.
2. STUDIES ON THE MECHANISM FOR THE ACTIVATION OF NF-kB IN FRTL-5 RAT THYROID CELLS
It is well known that cytokines such as TNF-a and interleukin-6 play important role for the development of autoimmune thyroid disorder. Also known is the fact that high levels of thyroid stimulating hormone aggravate the disorder. Since the effect of cytokines such as TNF-a is mediated through tranlocation of Nuclear factor k B (NF-kB) into the nucleus (activation), it is studied whether TSH modifies the activation of NF-kB by TNF-a. When FRTL-5 cells were not stimulated by TNF-a, no activation of NF-kB was observed. When the cells were stimulated with TNF-a alone, only p50-homodimer was observed in the nuclei. Combined treatment of the cells with TSH and TNF-a resulted in the appearance of p50-p65 heterodimer in the nuclei. Although p50, a subfamily of NF-kB,has DNA-binding activity, it lacks activation domain. Therefore, p50 homodimer is transcriptionally inactive. On the other hand, p65 has both DNA-binding and activation domains. Our finding that induction of p50-p65 heterodimer by TNF-a requires TSH indicates that suppression of TSH in may improve autoimmune thyroid disorder.
3. TSH-MEDIATED REGULATION OF THIOREDOXIN (TRX) AND REDOX FACTOR (Ref-1)
It has been recently shown that activation of NF-kB requires reduction by the enzymes such as TRX and Ref-1. As mentioned above, TSH modulates the activation of NF-kB TNF-a, it is investigated whether TSH regulates the expression of TRX and Ref-1 in FRTL-5 cells. It was demonstrated that TSH increases the expression of both TRX and Ref-1. Less

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] "Effect of aphidicolin on DNA synthesis in cultured human thyroid cells." Experimental clin Endocrinol Diabetes. 103. 88-93 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaya T,他: "Induction of transcription factor NF-kB by tumor necrosis factor α(TNFα)in human glioma cell lines : Correlation with TNFα Susceptibility." Environmental Medicine. 39. 13-16 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F,他: "Thyrotropin and insulin increase the binding activity of thyroid-transcription factors in FRTL-5 cells." Environmental Medicine. 39. 25-28 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F,他: "Differential induction of fos and jun family genes by thyrotropin in rat thyroid FRTL-5 cells." Thyroid. 6. 123-128 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] SEO Hisao: "Mutations of the thyroxine-binding globulin gene in Japanese." Internal Medicine. 35. 237-238 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato M,他: "Antioxidants inhibit tumor necrosis factor-α mediated stimulation of interleukin-8, monocyte chemoattractant protein-1, and collagenase expression in cultured human synovialcells." Journal of Rheumatology. 23. 432-438 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F and Seo H: "Thyrotropin and insulin increase the binding activity of thyroid-transcription factors in FRTL-5 cells." Environmental Medicine. 39(1). 25-28 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F,Miyazaki T and Seo H: "Differential induction of fos and jun family genes by thyrotropin in rat thyroid FRTL-5 cells." Thyroid. 6(2). 123-128 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato M,Miyazaki T,Nagaya T,Murata Y,Ida N,Maeda K,Seo H: "Antioxidants inhibit tumor necrosis factor-alpha mediated stimulation of interleukin-8, monocyte chemoattractant protein-1, and collagenase expression in cultured human synovial cells." Journal of Rheumatology. 23. 432-438 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaya T,Kopp P,Kitajima K,Jameson, JL,Seo H: "Second zinc finger mutants of thyroid hormone receptor selectively preserve DNA binding and heterodimerization but eliminate transcriptional activation." Biochemical and Biophysical Research Communications. 222. 524-530 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyazaki T,Kanou Y,Murata Y,Ohomori S,Niwa T,Maeda K,Yamamura H,Seo H: "Molecular cloning of a novel thyroid hormone-responsive gene, ZAKI-4, in human skin fibroblasts." Journal of Biological Chemistry. 271(24). 14567-14571 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nomura Y,Nagaya T,Tsukaguchi H,Takamatsu J,Seo H: "Amino acid substiutions of thyroid hormone receptor beta at codon 435 with resistance to thyroid hormone selectively alter homodimer formation." Endocrinology. 137(10). 4082-4086 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaya T,Nomura Y,Fujieda M,Seo H: "Heterodimerization preferences of thyroid hormone receptor alpha isoforms." Biochemical and Biophysical Research Communications. 226. 426-430 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F,Seo H: "Mediation of the hormone-and serum-dependent regulation of thyroglobulin gene expression by thyroid-transcription factors in rat thyroid FRTL-5 cells." Journal of Endocrinology. 150. 287-298 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kambe F,Nomura Y,Okamoto T,Seo H: "Redox regulation of thyroid-transcription factors, Pax-8 and TTF-1, is involved in their increased DNA-binding activities by thyrotropin in rat thyroid FRTL-5 cells." Molecular Endocrinology. 10. 801-812 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyazaki T,Murata Y,Ohmori S,Niwa T,Maeda K,Seo H: "Molecular cloning of rat ZAKI-4 gene." Environmental Medicine. 40(1)(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaya T,Fujieda M,Ohmori S,Seo H: "Molecular cloning of a thyroid hormone receptor interacting protein." Environmental Medicine. 40(1)(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Nagaya T,Nomura Y,Fujieda M,Yoshida J,Seo H: "Induction of transcription factor NF-kB by tumor necrosis factor alpha and interferon beta in human glioma cell lines." Environmental Medicine. 40(1)(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kikumori T,Kambe F,Asai T,Seo H: "Activation of nuclear factor-kappa B by tumor necrosis factor-alpha in rat thyroid FRTL-5 cells." Environmental Medicine. 40(1)(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Asai T,Kambe F,SAI Toshi, Kikumori T,Seo H,and SEO: "Effects of thyrotropin on Ref-1 mRNA and its protein levels in rat thyroid cell lines." Environmental Medicine. 40(1)(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Miyazaki T,他: "Molecular cloning of rat ZAKI-4 gene." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagaya T,他: "Molecular cloning of a thyroid hormone receptor interacting protein." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagaya T,他: "Induction of transcription factor NF-κB by tumor necrosis factor α and interferon β in human glioma cell lines." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kikumori T,他: "Activation of nuclear factor-kappa B by tumor necrosis factor-α in rat thyroid FRTL-5 cells." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Asai T,他: "Effects of thyrotropin on Ref-1 mRNA and its protein levels in rat thyroid cell lines." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kambe F,他: "Thioredoxin-mediated redox regulation of Pax-8." Environmental Medicine. 40(印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagaya T,他: "Second zinc finger mutants of thyroid hormorne receptor selectively preserve DNA binding and heterodimerization but eliminate transcriptional activation." Biochem Biophys Res Commun. 222. 524-530 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Miyazaki T,他: "Molecular cloning of a novel thyroid hormone-responsive gene,ZAKI-4,in human skin fibroblasts." J Biol Chem. 271. 14567-14571 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nomura Y,他: "Amino acid substiutions of thyroid hormone receptor β at codon 435 with resistance to thyroid hormone selectively alter homodimer formation." Endocrinology. 137. 4082-4086 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagaya T,他: "Heterodimerization preferences of thyroid hormone receptor α isoforms." Biochem Biophys Res Commun. 226. 426-430 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kambe F and Seo H: "Mediation of the hormone-and serum-dependent regulation of thyroglobulin gene expression by thyroid-transcription factors in rat thyroid FRTL-5 cells." Journal of Endocrinology. 150. 287-298 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kambe F,他: "Redox regulation of thyroid-transcription factors,Pax-8 and TTF-1,is involved in their increased DNA-binding activities by thyrotropin in rat thyroid FRTL-5 cells." Molecular Endocrinology. 10. 801-812 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fukushi Kambe他: "Differential induction of Fos and Jun family genes by thyrotropin in rat thyroid FRTL-5 cells." Thyroid. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 神部 福司他: "培養甲状腺細胞株FRTL-5における転写調節因子NF-kBのDNA結合能のホルモンによる変動" 名古屋大学環境医学研究所年報. 47(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 神部 福司他: "甲状腺特異的転写調節因子TTF-1、Pax-8のDNA結合能の酸化・還元制御" 名古屋大学環境医学研究所年報. 47(印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 菊森 豊根他: "ヒト甲状腺の癌および正常組織におけるmanganous superoxide dismutaseのmRNAの発現" 名古屋大学環境医学研究所年報. 47(印刷中). (1996)

    • Related Report
      1995 Annual Research Report

URL: 

Published: 1995-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi