| Project/Area Number |
03671141
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
内分泌・代謝学
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
ICHIKAWA Kazuo Shinshu Univ.Dept of Geriatrics, Lecturer, 医学部・附属病院老年科, 講師 (40159835)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HASHIZYUME Kiyoshi Shinshu Univ.Dept of Geriatrics, Professor, 医学部・附属病院老年科, 教授 (60092889)
|
|---|
| Project Period (FY) |
1991 – 1993
|
| Project Status |
Completed (Fiscal Year 1993)
|
| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
|
|---|
| Keywords | Thryoid hormone / Peroxisome / T3 responsive element / cellular T3 transport / Cell cycle / Nuclear T3 receptor / Cell proliferation / dRLh-84 cell / T3 responsive element / 細胞内T_3輸送 / 核T_3受容体 / 糖尿病 / リンゴ酸酵素 / 細胞核甲状腺ホルモン受容体 / 細胞質T3結合蛋白質 / 大腸菌発現ベクター / Non thyroidal illness / malic enzyme / 細胞格甲状腺ホルモン受容体 / インスリン / 大腸菌発現ベクタ- |
|---|
| Research Abstract |
1) Thyroid hormone-responsive rat hepatic t protein turned out to be a peroxisomal bifunctional enzyme. The amount of t Protein and the t Protein mRNA were increased after thyroidectomy and were decreased within 24 hrs after administration of small amount of triiodothyronine(T3) (0.3-1.0 mug/100 g body weight). By means of CAT assay, it was shown that 5' flanking region of the t protein gene contained negative T3 responsive element, indicating that negative regulation of the t protein by thyroid hormone was exerted at the transcriptional level.
2) We isolated cDNA fragment of rat hepatic nuclear n protein using antibody probe. It was shown that the induction of n protein by T3 was due to the increase of mRNA.However the idea that the cDNA fragment we isolated really encodes the n protein was not yet verified. For this purpose, we are planning to show that the amino acid sequences deduced from nucleotide sequences of the cDNA and those obtained from protein sequencing are the same.
3) We showed that carrier mediated and energy dependent cellular uptake of T3 is important source of nuclear T3. We showed that the nuclear entry of T3 is not solely via passive diffusion and is somehow regulated in the cell. It was also shown that the cellular transport of T3 is different from that of thyroxine(T4). Unlike T4, T3 transport is altered as the cells go through cell cycle. T3 is most actively transported into the cell at S phase when number of nuclear T3 receptor was increased. Additionally, T3 exerted proliferative effect on dRLh-84 cells through shortening of the S phase, suggesting that T3 action is enhanced in S phase due to increased number of receptor and enhanced uptake of T3.
|
