| Project/Area Number |
07457222
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagoya University |
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Principal Investigator |
SEO Hisao Nagoya Univ. Res. Inst. Environ. Med. Professor, 環境医学研究所, 教授 (40135380)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| 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)
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| Keywords | Nuclear 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 |
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| 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
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