Cell aging and vimentin glycation: Effects on the cytoskeleton and cell mechanics
细胞衰老和波形蛋白糖化:对细胞骨架和细胞力学的影响
基本信息
- 批准号:9134672
- 负责人:
- 金额:$ 21.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-01 至 2018-04-30
- 项目状态:已结题
- 来源:
- 关键词:AgeAgingAmino Acid SubstitutionAntibodiesBiochemicalBiological AssayCell AgingCellsComplementary DNAComputing MethodologiesCytoskeletal ProteinsCytoskeletonCytoskeleton AlterationDermalDiabetes MellitusEmbryoFibroblastsFluorescence Recovery After PhotobleachingGenomic InstabilityGlucoseGlyoxalGoalsHealthHumanImageryImmunoblottingIn VitroIndividualIntermediate Filament ProteinsIntermediate FilamentsLifeLysineMass Spectrum AnalysisMeasurementMechanicsMethodsMicrospheresMitochondriaMusOrganizational ChangeOryctolagus cuniculusOxidative StressPeptidesPhasePhased Innovation AwardsPost-Translational Protein ProcessingPreparationProcessPropertyProteinsReagentRheologyRoleSiteSkinStructureSystemTelomere ShorteningTimeTissuesVimentinage relatedagedbasecell ageglucose metabolismglycationinsightlaser tweezernormal agingparticlepolyclonal antibodyprotein structure functionresponsesenescencesugarsynthetic peptidevector
项目摘要
DESCRIPTION (provided by applicant): Aging involves the time-dependent accumulation of damage at the cellular level. While much is known about telomere shortening, genomic instability, oxidative stress, and mitochondrial malfunction, virtually nothing is known about age-dependent changes in cytoskeletal protein structure and function. An important protein modification associated with aging is the cumulative, non-enzymatic addition of sugar residues to proteins (i.e. glycation). Glycation is also a significant factor in diabetes, due to elevated glucose levels. It has recently been discovered that vimentin, a cytoskeletal intermediate filament (IF) protein, is a major target of glycation. The overarching goal of this proposal is to determine how glycation alters the normal structure and function of vimentin IF (VIF).This is of great importance to understanding the cellular basis of aging, as it is well known that IF are major factors in determining the mechanical properties of cells and tissues. It is also known that changes in the mechanical properties of cells accompany aging. In the exploratory (R21) phase of this project we will examine human skin fibroblasts to determine if the increasing age of the donor is accompanied by organizational changes in VIF networks. Studies will also be carried out to determine how experimentally induced glycation alters VIF network organization. Also during the R21 phase we will prepare antibodies specific for the regions that are glycated in vimentin and cDNAs expressing vimentin with amino acid substitutions for the relevant lysine residues. These reagents will be used for the R33 phase which will focus on determining the effects of glycation on the dynamics of vimentin IF, on their subcellular organization and on their
specific roles in altering the micromechanical properties of cells. This will involve using both state of the art live cell assays; and in vitro analyses of the effects of glycation on vimentin assembly, structure, and mechanical properties. Some of these studies will be carried out with a group of collaborators that we have enlisted for this project. Finally, attempts will be made to correlate the changes in vimentin glycation with age related parameters of tissues obtained from young and old mice. The studies proposed will provide important new insights into how age-dependent protein glycation alters the organization and expression of the vimentin cytoskeleton and how these alterations impact the micromechanical properties of the cell.
描述(由适用提供):衰老涉及在细胞水平上损害的时间依赖性积累。虽然对端粒缩短,基因组不稳定性,氧化应激和线粒体功能障碍知之甚少,但实际上对细胞骨架蛋白质结构和功能的年龄依赖性变化几乎一无所知。与衰老相关的重要蛋白质修饰是累积的,非酶添加糖保留在蛋白质中(即糖基化也是糖尿病中的重要因素,这是由于葡萄糖水平升高而导致的。最近已经发现,在骨骼中间丝状(如果是一个主要的目标),则发现了cytoskembection Middiate-Middiate Mideidiate Mideipart(IF),这是一个主要的目标。 normal structure and function of vimentin IF (VIF).This is of great importance to understand the cellular basis of aging, as it is well known that IF are major factors in determining the mechanical properties of cells and tissues. It is also known that changes in the mechanical properties of cells involved aging. In the exploratory (R21) phase of this project we will examine human skin fibroblasts to determine if the increasing age of the donor is accomplished by organizational changes in VIF网络还将进行研究,以确定实验诱导的糖化如何改变VIF网络组织。同样在R21阶段,我们将制备针对与氨基酸取代的波形蛋白和cDNA中的区域的特异性抗体,以用于相关的赖氨酸保留率。这些试剂将用于R33阶段,该试剂将侧重于确定糖化对波形蛋白动力学的影响,如果对其亚细胞组织以及其亚细胞组织的影响
在改变细胞的微力特性中的特定作用。这将涉及使用两种最新现场细胞测定法。以及糖基化对波形蛋白组装,结构和机械性能的影响的体外分析。其中一些研究将与我们为该项目征募的一组合作者进行。最后,将尝试将波形蛋白糖基化的变化与从小小鼠获得的组织的年龄相关参数相关联。提出的研究将提供重要的新见解,以了解年龄依赖性蛋白质糖基化如何改变波形蛋白细胞骨架的组织和表达,以及这些改变如何影响细胞的微力特性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROBERT D GOLDMAN其他文献
ROBERT D GOLDMAN的其他文献
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{{ truncateString('ROBERT D GOLDMAN', 18)}}的其他基金
Super-resolution microscopy of nuclear lamin and spindle envelope/matrix function
核纤层和纺锤体包膜/基质功能的超分辨率显微镜
- 批准号:
8489713 - 财政年份:2013
- 资助金额:
$ 21.14万 - 项目类别:
Super-resolution microscopy of nuclear lamin and spindle envelope/matrix function
核纤层和纺锤体包膜/基质功能的超分辨率显微镜
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8666780 - 财政年份:2013
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$ 21.14万 - 项目类别:
Super-resolution microscopy of nuclear lamin and spindle envelope/matrix function
核纤层和纺锤体包膜/基质功能的超分辨率显微镜
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8893760 - 财政年份:2013
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$ 21.14万 - 项目类别:
Regulation and Function of Intermediate Filaments in Cell Mechanics
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8500383 - 财政年份:2011
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$ 21.14万 - 项目类别:
Regulation and Function of Intermediate Filaments in Cell Mechanics
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- 批准号:
8847726 - 财政年份:2011
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$ 21.14万 - 项目类别:
Regulation and Function of Intermediate Filaments in Cell Mechanics
细胞力学中中间丝的调节和功能
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8078537 - 财政年份:2011
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$ 21.14万 - 项目类别:
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8142481 - 财政年份:2011
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$ 21.14万 - 项目类别:
Regulation and Function of Intermediate Filaments in Cell Mechanics
细胞力学中中间丝的调节和功能
- 批准号:
8665988 - 财政年份:2011
- 资助金额:
$ 21.14万 - 项目类别:
Regulation and Function of Intermediate Filaments in Cell Mechanics
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8471253 - 财政年份:2011
- 资助金额:
$ 21.14万 - 项目类别:
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