Aging of the subcellular muscle proteome

亚细胞肌肉蛋白质组的衰老

• 批准号: 6950861
• 负责人: EDGAR A ARRIAGA
• 金额: $ 14.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950861
• 关键词: aging; biopsy; carbonyl compound; clinical research; free radical oxygen; intracellular; laboratory rat; liquid chromatography mass spectrometry; longitudinal animal study; mitochondria; oxidative stress; posttranslational modifications; protein quantitation /detection; proteomics; striated muscles

DESCRIPTION (provided by applicant): The specificity of age-related oxidative damage to proteomes is largely unknown. Our long-term goal is to develop new proteomic strategies capable of identifying proteins susceptible to such damage. In this exploratory R21 application, our short-term goal is to use the concept of subcellular proteomes, carbonyl immuno-capture, and ICAT technology to identify (and discover) age-related carbonyl-associated proteins in muscle mitochondria. We will use the Fisher 344 rat as an animal model. We will compare the proteomes of two muscles whose functions decline differently with aging, the soleus and semimembranosus. While the soleus is significantly dependent on mitochondria for ATP production, the semimembranosus relies on glycolysis as a source of ATP. As a result, it is hypothesized that different ROS production patterns will cause different protein oxidative damage in these two muscles. Two studies are proposed: (1) direct comparison of carbonyl-associated proteins in the two muscle types at 6 and 28 months of age; (2) a longitudinal study with muscle sampling from the same animal at three different ages. Sample limitations in the second study will be addressed by using FT-ICR-MS and CE-LIF.

描述（由申请人提供）：与年龄相关的蛋白质组氧化损伤的特异性很大程度上未知。我们的长期目标是开发新的蛋白质组学策略，能够识别易受此类损伤的蛋白质。在这个探索性的 R21 应用中，我们的短期目标是利用亚细胞蛋白质组、羰基免疫捕获和 ICAT 技术的概念来识别（和发现）肌肉线粒体中与年龄相关的羰基相关蛋白。我们将使用 Fisher 344 大鼠作为动物模型。我们将比较比目鱼肌和半膜肌这两种肌肉的蛋白质组，这两种肌肉的功能随着年龄的增长而不同程度地下降。比目鱼肌明显依赖线粒体来产生 ATP，而半膜肌则依赖糖酵解作为 ATP 的来源。因此，推测不同的 ROS 产生模式将在这两块肌肉中造成不同的蛋白质氧化损伤。提出了两项​​研究：（1）直接比较 6 个月和 28 个月龄时两种肌肉类型中的羰基相关蛋白； (2) 对同一动物在三个不同年龄进行肌肉取样的纵向研究。第二项研究中的样本限制将通过使用 FT-ICR-MS 和 CE-LIF 来解决。

项目成果

Preparative peptide isoelectric focusing as a tool for improving the identification of lysine-acetylated peptides from complex mixtures.

制备型肽等电聚焦作为改进从复杂混合物中鉴定赖氨酸乙酰化肽的工具。

• 发表时间: 2007-05
• 影响因子: 4.4
• 作者: Xie, Hongwei;Bandhakavi, Sricharan;Roe, Mikel R;Griffin, Timothy J
• 通讯作者: Griffin, Timothy J

Advancing mammalian cell culture engineering using genome-scale technologies.

利用基因组规模技术推进哺乳动物细胞培养工程。

• 发表时间: 2007-09
• 影响因子: 17.3
• 作者: Griffin, Timothy J;Seth, Gargi;Xie, Hongwei;Bandhakavi, Sricharan;Hu, Wei
• 通讯作者: Hu, Wei

Proteomic mapping of 4-hydroxynonenal protein modification sites by solid-phase hydrazide chemistry and mass spectrometry.

• DOI: 10.1021/ac0617971
• 发表时间: 2007-04-17
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Mikel R. Roe;Hongwei Xie;S. B;hakavi;hakavi;T. Griffin
• 通讯作者: T. Griffin

iTRAQ reagent-based quantitative proteomic analysis on a linear ion trap mass spectrometer.

在线性离子阱质谱仪上进行基于 iTRAQ 试剂的定量蛋白质组分析。

• DOI: 10.1021/pr070291b
• 发表时间: 2007-09-29
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: T. Griffin;Hongwei Xie;S. B;hakavi;hakavi;Jonathan Popko;Archana Mohan;J. Carlis;LeeAnn Higgins
• 通讯作者: LeeAnn Higgins