Cardiomyocyte Function and Trace Element (TE) Status during Aging: Role of Proteostasis
衰老过程中心肌细胞功能和微量元素 (TE) 状态:蛋白质稳态的作用
基本信息
- 批准号:448242516
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Units
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Iron (Fe) is essential for normal cellular functioning, but in excess, labile reactive Fe enhances oxidative stress, often resulting in a free radical-induced cell death. On the other hand, Fe is crucial for the energy production of cells, especially in cardiomyocytes possessing a high energy demand. In cardiomyocytes, Fe is also required for myoglobin function providing intracellular oxygen transport. Therefore, cardiomyocytes are highly vulnerable to disturbances of Fe metabolism. The functionality of the Fe metabolism is ensured by a number of proteins, which undergo a permanent turnover. Aging is characterized by malfunction of protein turnover, which is mainly due to reduced responses of the ubiquitin-proteasomal system and the autophagy-lysosomal system. This is a dominating process in aging and, therefore, a decline of proteostasis is a hallmark of the aging process. My group has been investigating the degradation of oxidatively modified proteins during aging, including the degradation of proteins of the Fe metabolism, and the regulation of redox-mediated protein degradation for several years. The goal of this project is to systematically investigate, how age-associated changes in proteostasis, in particular proteolytic pathways, effect trace element (TE) status and Fe metabolism-related proteins in cardiomyocytes in relation to cellular function. We will a) establish a correlation between proteolytic pathways and TE-binding and -regulating proteins in aging cardiomyocytes; b) test whether aging per se or hypertrophy as a known phenomenon of aging in cardiomyocytes is the driving factor for age-related TE (Fe) and functional disturbance; and c) test the interaction between various TE occurring during aging or inflammation and Fe metabolism. This will be done in the context with TE profiles of other organs and translated to the human situation.
铁(Fe)对正常细胞功能至关重要,但过量时,不稳定的反应性Fe会增强氧化应激,通常导致自由基诱导的细胞死亡。另一方面,Fe对于细胞的能量产生至关重要,特别是在具有高能量需求的心肌细胞中。在心肌细胞中,Fe也是肌红蛋白提供细胞内氧转运功能所必需的。因此,心肌细胞非常容易受到铁代谢紊乱的影响。铁代谢的功能性由许多蛋白质确保,这些蛋白质经历永久性周转。衰老的特征是蛋白质周转功能障碍,这主要是由于泛素-蛋白酶体系统和自噬-溶酶体系统的反应降低。这是衰老的主要过程,因此,蛋白质稳态的下降是衰老过程的标志。我的小组几年来一直在研究衰老过程中氧化修饰蛋白质的降解,包括铁代谢蛋白质的降解,以及氧化还原介导的蛋白质降解的调节。该项目的目标是系统地研究,如何与年龄相关的蛋白质稳态的变化,特别是蛋白水解途径,影响微量元素(TE)的状态和铁代谢相关的蛋白质在心肌细胞的细胞功能。我们将a)建立衰老心肌细胞中蛋白水解途径与TE结合和调节蛋白之间的相关性; B)测试衰老本身或肥大(心肌细胞中已知的衰老现象)是否是年龄相关TE(Fe)和功能障碍的驱动因素;和c)测试衰老或炎症期间发生的各种TE与铁代谢之间的相互作用。这将在其他器官的TE曲线的背景下完成,并转化为人体情况。
项目成果
期刊论文数量(0)
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专利数量(0)
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Professor Dr. Tilman Grune其他文献
Professor Dr. Tilman Grune的其他文献
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{{ truncateString('Professor Dr. Tilman Grune', 18)}}的其他基金
Understanding the effect of a ketogenic diet in colitis
了解生酮饮食对结肠炎的影响
- 批准号:
397437773 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Research Grants
Fate of nitrated proteins: denitration or degradation?
硝化蛋白质的命运:脱硝还是降解?
- 批准号:
257921205 - 财政年份:2014
- 资助金额:
-- - 项目类别:
Research Grants
Lipofuszinbildung in seneszenten Zellen: Rolle des lysosomalen Vitamin E und mitochondrialer Antioxidantien
衰老细胞中脂褐质的形成:溶酶体维生素 E 和线粒体抗氧化剂的作用
- 批准号:
162900865 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Research Grants
Regulation of the ubiquitin-proteasome-system during oxidative stress
氧化应激过程中泛素蛋白酶体系统的调节
- 批准号:
5249904 - 财政年份:2000
- 资助金额:
-- - 项目类别:
Priority Programmes
Tau-Modification and Oxidative Stress
Tau 修饰和氧化应激
- 批准号:
5250812 - 财政年份:2000
- 资助金额:
-- - 项目类别:
Priority Programmes
Microglialer Abbau modifizierter extrazellulärer Proteine
修饰细胞外蛋白的小胶质细胞降解
- 批准号:
5221197 - 财政年份:2000
- 资助金额:
-- - 项目类别:
Research Grants
Dietary fat and adipocyte-macrophage interaction
膳食脂肪和脂肪细胞-巨噬细胞相互作用
- 批准号:
454257572 - 财政年份:
- 资助金额:
-- - 项目类别:
Research Grants
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Roles of trace amines in recovery of sensorimotor and vascular function after spinal cord injury.
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