Molecular mechanisms of dehydroepiandrosterone sulfate action on skeletal muscle cells

硫酸脱氢表雄酮对骨骼肌细胞作用的分子机制

• 批准号: 12670627
• 负责人: FURUTAMA Daisuke
• 金额: $ 1.92万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670627/
• 关键词: steroid; nuclear receptor; transcription factor; skeletal muscle; liver; myotonic dystrophy

We investigated whether DHEA or DHEA-S affected the activities of nuclear receptors, with special reference to CARβ. Administration of DHEA or DHEA-S enhanced the DNA binding of hepatic nuclear extracts to responsive elements for the retinoic acid receptor (RARE), the retinoic acid receptor β2 (β RARE) and the peroxisome proliferator activated receptor (HD-PPRE). The bound complexes were shown to the CARβ-RXR heterodimer by antibody-supershift assays. The expression of a target gene of CARβ, Cyp2b10, was increased in liver by DHEA or DHEA-S treatment, suggesting that DHEA or DHEA-S actually activated CARβ in vivo. It was suggested that the metabolic conversion of DHEA, DHEA-S to CARβ ligands could occur in vivo and the metabolites could regulate the expression of CARβ target gene expression. Our results provide new insights into the in vivo relationship between DHEA/ DHEA-S and CARβ activation.

我们研究了DHEA或DHEA- s是否影响核受体的活性，特别参考了CARβ。DHEA或DHEA- s可增强肝核提取物与维甲酸受体（RARE）、维甲酸受体β2 （β RARE）和过氧化物酶体增殖物激活受体（HD-PPRE）响应元件的DNA结合。结合的复合物通过抗体超移实验显示为car - β- rxr异源二聚体。在DHEA或DHEA- s处理下，肝脏中CARβ靶基因Cyp2b10的表达增加，表明DHEA或DHEA- s在体内实际上激活了CARβ。提示DHEA、DHEA- s在体内可代谢转化为CARβ配体，其代谢产物可调节CARβ靶基因的表达。我们的研究结果为DHEA/ DHEA- s与CARβ活化之间的体内关系提供了新的见解。

项目成果

大澤仲昭: "DHEA,DHEA-Sと筋疾患"ホルモンと臨床. 48巻・9号. 783-790 (2000)

Nakaaki Osawa：“DHEA、DHEA-S 和肌肉疾病”《激素与临床研究》，第 48 卷，第 9 期。783-790 (2000)。

Mehrdad Khajavi, Ana M. Tari, Nalini B. Patel, Kuniko Tsuji, Doris R. Siwak, Marvin L. Meistrich, Nicolas H.A. Terry, Tetsuo Ashizawa: "'Mitotic drive' of expanded CTG repeats in myotonic dystrophy type 1 (DM1)"Human Molecular Genetics. vol. 10. 855-863 (

Mehrdad Khajavi、Ana M. Tari、Nalini B. Patel、Kuniko Tsuji、Doris R. Siwak、Marvin L. Meistrich、Nicolas H.A.

The International Myotonic Dystrophy Consortium (IDMC): "New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1)"Neurology. 54. 1218-1221 (2000)

国际强直性肌营养不良联盟 (IDMC)：“强直性肌营养不良 1 型 (DM1) 的新命名法和 DNA 检测指南”神经病学。

Atsushi Fujita, Daisuke Furutama, Toshifumi Tanaka, Reiko Sakai, Akio Koyama, Toshiaki Hanafusa, Tomoaki Mitsuhashi, Nakaaki Ohsawa: "Treatment with dehydroepiandrosterone(DHEA) and DHEA sulfate enhances DNA binding activity of CARβ(consititutive androsta

Atsushi Fujita、Daisuke Furutama、Toshifumi Tanaka、Reiko Sakai、Akio Koyama、Toshiaki Hanafusa、Tomoaki Mitsuhashi、Nakaaki Ohsawa：“用脱氢表雄酮 (DHEA) 和 DHEA 硫酸盐治疗可增强 CARβ（组成型雄雄激素）的 DNA 结合活性

The International Myotonic Dystrophy Consortium (IDMC): "New nomenclature and DNA testing guidance for myotonic dystrophy type 1 (DM1)"FEBS Letters. vol. 532. 373-378 (2002)

国际强直性肌营养不良联盟 (IDMC)：“强直性肌营养不良 1 型 (DM1) 的新命名法和 DNA 检测指南”FEBS 快报。