Biomarkers of Thyronamine Action (BioTAct)

甲状腺胺作用的生物标志物 (BioTAct)

• 批准号: 221224449
• 负责人: Professor Dr. Lutz Schomburg
• 金额: --
• 依托单位: Institut für Experimentelle Endokrinologie (CVK)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/221224449?language=en
• 关键词: Biomarkers; Thyronamine; Action; BioTAct

Thyronamines are a recently re-discovered class of endogenous hormones of potential high importance for human health and medical applications. Besides some initial reports on impressively strong physiological effects in animal models, the exact molecular mode of action of the different thyronamines is not understood. Thyronamines can counteract the effects of the classical thyroid hormones T3 and T4. As an example, injection of 3-iodothyronamine (3-T1AM) into mice reduces glucose and increases lipid metabolism, and reduces metabolic rate, body temperature, ino- and chronotropy and other measures of energy turnover. Besides these systemic effects on the organism, the responsible signalling pathways are not understood as well as molecular biomarkers of thyronamine (TAM) action are missing. We have identified TAM-responsive cell models. Now we aim to employ a systematic screening approach to identify molecular targets of TAM action. Pathway reporter assays, global gene expression analyses, candidate gene approaches and biological readouts of cell differentiation will be combined for bio-marker identification. Molecular candidates will be validated and used to track the pathways responsible for their TAM-dependent regulation. Long-term aim is the identification of suitable biomarkers that can be measured from serum samples of experimental animals and humans as diagnostic readouts for the individual TAM status.

甲状腺激素是最近重新发现的一类内源性激素，对人类健康和医疗应用具有潜在的重要意义。除了一些关于动物模型中令人印象深刻的强烈生理效应的初步报道外，不同甲状腺原胺的确切分子作用模式尚不清楚。甲状腺激素可以抵消经典的甲状腺激素T3和T4的影响。例如，向小鼠体内注射3-碘甲状腺原胺(3-T1AM)可降低葡萄糖和增加脂肪代谢，并降低代谢率、体温、变态和变时性等能量周转指标。除了对生物体的这些全身性影响外，负责的信号通路还不清楚，也缺乏甲状腺原氨酸()作用的分子生物标记物。我们已经确定了反应的细胞模型。现在我们的目标是采用一种系统的筛选方法来寻找作用的分子靶点。途径报告分析、全球基因表达分析、候选基因方法和细胞分化的生物学读数将结合起来用于生物标记鉴定。候选分子将得到验证，并用于追踪负责其依赖调控的途径。长期目标是确定合适的生物标记物，这些标记物可以从实验动物和人类的血清样本中测量出来，作为状态的诊断读数。