Multiple physiological roles of cytosolic 3,5,3'-triiodothyronine binding protein (CTBP)

胞质 3,5,3-三碘甲状腺原氨酸结合蛋白 (CTBP) 的多种生理作用

• 批准号: 17590957
• 负责人: HASHIZUME Kiyoshi
• 金额: $ 2.3万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590957/
• 关键词: thyroid hormone; CRYM; mu-crystallin; ABR; NADPH; knockout mouse; 3,5,3'-triiodo-L-thyronine

Previously, we identified NADPH-dependent cytosolic T3 binding protein (CTBP) in rat cytosol. CTBP is identical to m-crystallin (CRYM). Recently, CRYM mutations were found in patients with non-syndromic hereditary deafness. Although it has been established that CRYM plays pivotal roles in reserving and transporting T3 into the nuclei in vitro and has a clinical impact on hearing ability, the precise functions of CRYM remain to be elucidated in vivo.To further investigate the in vivo functions of CRYM gene products, we have generated mice with targeted disruption of the CRYM gene, which abrogates the production of CRYM. CRYM knockout loses the NADPH-dependent T3 binding activity in the cytosol of the brain, kidney, heart, and liver. At the euthyroid state, knockout significantly suppresses the serum concentration of T3 and T4 despite normal growth, heart rate and hearing ability. The disruption of the gene does not alter the expression of TSHb mRNA in the pituitary gland or glutathione S transferase alpha 2 and deiodinase 1 mRNAs in either the liver or kidney. When radiolabeled T3 is injected intravenously, labeled T3 rapidly enters into then escapes from the tissues in CRYM-knockout mice. These data suggest that because of rapid T3 turnover, disruption of the CRYM gene decreases T3 concentrations in tissues and serum without alteration of peripheral T3 action in vivo.

以前，我们确定了NADPH依赖的胞质T3结合蛋白（CTBP）在大鼠胞质溶胶。CTBP与m-晶状体蛋白（M-crystallin，MRM）相同。近年来，在非综合征型遗传性耳聋患者中发现了MRM突变。虽然它已被确定，在保留和运输T3到细胞核中的体外发挥关键作用，并有听力的临床影响，精确的功能，仍有待阐明在vivo.To进一步研究在体内的功能，我们已经产生了小鼠的靶向破坏的FAMIM基因，废除生产FAMIM。敲除NADPH M会丧失脑、肾、心脏和肝的胞质溶胶中的NADPH依赖性T3结合活性。在甲状腺功能正常的状态下，敲除显著抑制血清中T3和T4的浓度，尽管生长、心率和听力正常。该基因的破坏不会改变垂体中TSHb mRNA的表达或肝脏或肾脏中谷胱甘肽S转移酶α 2和脱碘酶1 mRNA的表达。当静脉注射放射性标记的T3时，标记的T3迅速进入并从IgM敲除小鼠的组织中逃逸。这些数据表明，由于T3的快速周转，破坏的CD 4 M基因降低T3浓度在组织和血清中，而不改变外周T3的行动在体内。

项目成果

Metobolic syndrome and age-related dementia : endocrinological aspects of adaptation to aging.

代谢综合征和年龄相关性痴呆：适应衰老的内分泌方面。

• 发表时间: 2006
• 期刊: Mech Ageing Dev 127
• 作者: Hashizume K;Suzuki S;Hara M;Komatsu A;Yamashita K
• 通讯作者: Yamashita K

Metabolic syndrome and age-related dementia : Endocrinological aspects of adaptation to aging

代谢综合征和年龄相关性痴呆：适应衰老的内分泌方面

• 发表时间: 2006
• 期刊: Mech Ageing Dev 127
• 作者: Hashizume K;Suzuki S;Hara M;Komatsu A;Yamashita K
• 通讯作者: Yamashita K

μ-crystallin as an intracellular 3,5,3' triiodothyronine holder in vivo

μ-晶状体蛋白作为体内细胞内 3,5,3 三碘甲状腺氨酸支架

• 发表时间: 2007
• 期刊: Molecular Endocrinology 21
• 作者: S.Suzuki;N.Suzuki;Jun-ichirou Mori;A.Oshima;S.Usami;K.Hashizume
• 通讯作者: K.Hashizume

Endocrinological aspects of aging : Adaptation to and acceleration of aging by the endocrine system.

衰老的内分泌方面：内分泌系统对衰老的适应和加速。

• 发表时间: 2006
• 期刊: Geriatr Gerontol Int 6
• 作者: Hashizume K;Suzuki S;Takeda T;Shigematsu S;Ichikawa K;Koizumi Y
• 通讯作者: Koizumi Y

Inhibition of LXRalpha signaling by vitamin D receptor : possible role of VDR in bile acid synthesis

维生素 D 受体抑制 LXRα 信号传导：VDR 在胆汁酸合成中的可能作用

• 发表时间: 2006
• 期刊: Biochem Biophys Res Commun 351
• 作者: Jiang W;Miyamoto T;Kakizawa T;Nishio SI;Oiwa A;Takeda T;Suzuki S;Hashizume K
• 通讯作者: Hashizume K