Identification of thyroid hormone response element of atrial natriuretic factor

心房钠尿因子甲状腺激素反应元件的鉴定

• 批准号: 04833025
• 负责人: MATSUBARA Hiroaki
• 金额: $ 1.22万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04833025/
• 关键词: Thyroid hormone; atrial natriuretic factor; gene expression; atrial myocyte; cardiac myocyte; 心房性ナトリウム利尿ホルモン

Atrial natriuretic factor(ANF) is a hormone that dilates vasculature and induces natriuresis, and is synthesized and secreted from atrial myocytes. We have demonstrated for the first time that thyroid hormone(T_3)stimulates synthesis and release of ANF from atrial myocytes, and that its stimulatory effect is mediated through gene transcription. To characterize the T_3 response element(TRE)of ANF promoter, we deletion-mutated 2.4Kb of the 5' flanking region toward the downstream and fucked 5' end of chrolamphenicol acetyltransferase(CAT)gene. These deletion-mutated CAT constructs were transfected into the atrial myocytes. We identified the TRE in the region located in -108 to -68bp. The gel shift assay demonstrates that this region binds to the nuclear factor induced by the addition of T_3 and no retarded band was observed in the nuclear extract in the absence of T_3. No consensus TRE motif previously recognized was detected in -108 to -68. Thus, we characterized the TRE specific for ANF gene in -108 to -68 from the transcription site, the sequence of which conferred the T_3 responsiveness to the ANF gene.

心钠素(ANF)是一种扩张血管、诱导利钠的激素，由心房肌细胞合成和分泌。我们首次证实了甲状腺激素(T_3)刺激心房肌细胞合成和释放心钠素，其刺激作用是通过基因转录介导的。为了研究ANF启动子的T_3反应元件(TrE)，我们对其下游5‘侧翼区2.4Kb进行了缺失突变，并对CAT基因5’端进行了功能突变。将这些缺失突变的CAT载体导入心房肌细胞。我们在-108到-68个碱基的区域中确定了TrE。凝胶漂移分析表明，该区域与添加T_3诱导的核因子结合，在没有T_3的情况下，核提取液中没有观察到延迟带。在-108到-68之间没有发现一致的tre基序。因此，我们从转录位点鉴定了ANF基因In-108到-68的tre，其序列推测了ANF基因的T_3反应性。

项目成果

松原弘明 他7名: "Role of calcium and protein kinase Cin ANP secretion by cultured rat cardiocytes" Am J Physiol. 24. H405-H409 (1988)

Hiroaki Matsubara 和其他 7 人：“钙和蛋白激酶 C 在培养的大鼠心肌细胞分泌 ANP 中的作用”Am J Physiol 24. H405-H409 (1988)

Matsubara H.et al.: "Heart with circulatory failure secretes and processes atrial natriuretic peptide in a manner different from normal heart" Clin Cardiol. 11. 197-203 (1988)

Matsubara H.等人：“循环衰竭的心脏以与正常心脏不同的方式分泌和处理心房钠尿肽”Clin Cardiol。

Matsubara H.et al.: "Role of atrial natriuretic polypeptides for exaggerated natriuresis in essential hypertension" Am J Cardiol. 60. 708-714 (1987)

Matsubara H.等人：“心房钠尿肽对原发性高血压中过度钠尿的作用”Am J Cardiol。

松原弘明 他6名: "Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat" Biochem Biophys Res Commun. 145. 336-343 (1987)

Hiroaki Matsubara 等 6 人：“类固醇和甲状腺激素对培养的大鼠心房肌细胞合成心钠素的影响”Biochem Biophys Res Commun. 145. 336-343 (1987)。

Matsubara H.et al.: "Diabetes-induced alterations in atrial natriuretic peptide gene expression in Wistar-Kyoto and spontaneously hypertensive rats" Circ Res. 67. 803-813 (1990)

Matsubara H.等人：“Wistar-Kyoto 和自发性高血压大鼠中糖尿病引起的心房钠尿肽基因表达的改变”Circ Res。