Lens crystallins: spatial location and properties in the ICR/f rat cataract model

晶状体蛋白:ICR/f 大鼠白内障模型中的空间位置和特性

基本信息

  • 批准号:
    8117497
  • 负责人:
  • 金额:
    $ 17.91万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-01 至 2013-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Maintaining the function of the lens ?A- and ?B-crystallins with aging is the key event in preventing cataracts. Although it is well known that ?A- and ?B-crystallins undergo extensive modifications (crosslinking, glycation, oxidation, phosphorylation and truncation) over a lifetime, it is less clear when these modifications occur or in which zone of the lens (nuclear and cortical regions). This application takes advantage of two experimental approaches: (1) the ICR/f rat, a model of age-related cataracts, that spontaneously forms cataracts witihin 10- 11 weeks of life, and (2) mass spectrometry imaging of sections of the lens that allows determination of the spatial distribution (at 100 micron resolution) of individual ?A- and ?B-crystallins. In preliminary experiments we have successfully developed methods for obtaining tissue sections of the rat lens, for spotting with matrix robotically and obtaining images of the distribution of lens proteins. The goal of this application is to examine two hypotheses: (1) ?A- and ?B-crystallins undergo modifications, particularly truncation, that cause them to be specifically localized within the lens at particular stages of development, processes that are altered by intervention with genistein and disulfiram, and (2) that the modifications of the ?A- and ?B-crystallins decrease their solubility, thereby accounting for their localization. In the first aim, ICR/f rats and mass spectrometry imaging will be used to determine the effect of genistein in the diet and disulfiram by eye drops on the type and timing of ?A- and ?B-crystallins' truncation/modifications and distribution during cataract development. Lenses from untreated ICR/f rats and Wistar rats (the latter do not have cataracts) will be examined to determine the onset of the appearance of specific cataract-associated ?A- and ?B-crystallin fragments. In the second aim, selected truncated ?A- and ?B-crystallins (e.g., m/z 6409), showing marked regional distribution by mass spectrometry imaging, will be extracted from the lens (into water-soluble and water-insoluble/urea- soluble fractions). These will be purified using chromatographic and electrophoretic techniques and then fully characterized by determination of their accurate molecular weights, sequence and modifications. These studies will highlight the solubility/function information embedded in the sequence of a protein that has such an extended lifetime and also establish the ICR/f rat as a convenient test bed for exploring the mechanism of interventions to prevent/delay cataracts. PUBLIC HEALTH RELEVANCE: 50% of the general population who reach 70 years of age will have required lens replacement surgery as well as having previous diminished vision. Given the increasing proportion of the elderly in the USA and the importance of sustaining quality of life, interventions to reduce the risk of cataracts are warranted. The ICR/f rat is a model to evaluate both new therapeutic interventions as well as risk factors in dietary supplements.
描述(由申请人提供):维持镜头的功能?A- and ?随着年龄的增长,b晶体蛋白是预防白内障的关键因素。虽然大家都知道?A- and ?b -结晶蛋白在一生中经历广泛的修饰(交联、糖基化、氧化、磷酸化和截断),这些修饰何时发生或发生在晶体的哪个区域(核区和皮质区)尚不清楚。该应用利用了两种实验方法:(1)ICR/f模型,这是一种年龄相关性白内障模型,在10- 11周内自发形成白内障;(2)晶状体部分的质谱成像,可以确定个体的空间分布(100微米分辨率)?A和b晶体蛋白。在初步的实验中,我们已经成功地开发了获得大鼠晶状体组织切片的方法,用于机器人标记基质和获得晶状体蛋白质分布的图像。本应用程序的目标是检验两个假设:(1)?A- and ?b -晶体蛋白经过修饰,特别是截断,导致它们在特定发育阶段特异性地定位在晶状体内,这一过程通过染料木素和双硫仑的干预而改变,并且(2)?A- and ?b晶蛋白降低了它们的溶解度,从而解释了它们的定位。在第一个目标中,将使用ICR/f大鼠和质谱成像来确定饮食中的染料木素和滴眼液中的双硫仑对?A- and ?白内障发育过程中b -晶状体蛋白的截断/修饰及分布。将对未经治疗的ICR/f大鼠和Wistar大鼠(后者没有白内障)的晶状体进行检查,以确定特定白内障相关?A- and ?B-crystallin碎片。在第二个目标中,选择截断?A- and ?b -晶体蛋白(例如,m/z 6409)通过质谱成像显示出明显的区域分布,将从透镜中提取(分为水溶性和水不溶性/尿素溶性部分)。这些将使用色谱和电泳技术纯化,然后通过测定其准确的分子量、序列和修饰来充分表征。这些研究将突出嵌入在具有如此长寿命的蛋白质序列中的溶解度/功能信息,并将ICR/f鼠建立为探索预防/延迟白内障干预机制的方便试验平台。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

STEPHEN BARNES其他文献

STEPHEN BARNES的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('STEPHEN BARNES', 18)}}的其他基金

"UAB Metabolomics Workshop: from design to decision"
“UAB代谢组学研讨会:从设计到决策”
  • 批准号:
    8717686
  • 财政年份:
    2012
  • 资助金额:
    $ 17.91万
  • 项目类别:
"UAB Metabolomics Workshop: from design to decision"
“UAB代谢组学研讨会:从设计到决策”
  • 批准号:
    8416292
  • 财政年份:
    2012
  • 资助金额:
    $ 17.91万
  • 项目类别:
"UAB Metabolomics Workshop: from design to decision"
“UAB代谢组学研讨会:从设计到决策”
  • 批准号:
    8912500
  • 财政年份:
    2012
  • 资助金额:
    $ 17.91万
  • 项目类别:
Lens crystallins: spatial location and properties in the ICR/f rat cataract model
晶状体蛋白:ICR/f 大鼠白内障模型中的空间位置和特性
  • 批准号:
    7976943
  • 财政年份:
    2010
  • 资助金额:
    $ 17.91万
  • 项目类别:
Lens crystallins: spatial location and properties in the ICR/f rat cataract model
晶状体蛋白:ICR/f 大鼠白内障模型中的空间位置和特性
  • 批准号:
    8134148
  • 财政年份:
    2010
  • 资助金额:
    $ 17.91万
  • 项目类别:
5500 Q-Trap Mass Spectrometer
5500 Q-Trap 质谱仪
  • 批准号:
    7794200
  • 财政年份:
    2010
  • 资助金额:
    $ 17.91万
  • 项目类别:
Skin Proteomics Core
皮肤蛋白质组学核心
  • 批准号:
    7677162
  • 财政年份:
    2009
  • 资助金额:
    $ 17.91万
  • 项目类别:
Urinary peptide excretion and onset of puberty
尿肽排泄和青春期开始
  • 批准号:
    7846995
  • 财政年份:
    2009
  • 资助金额:
    $ 17.91万
  • 项目类别:
Bioanalytical CoreBioanalytical Core
生物分析核心Bioanalytical Core
  • 批准号:
    8899511
  • 财政年份:
    2008
  • 资助金额:
    $ 17.91万
  • 项目类别:
Urinary peptide excretion and onset of puberty
尿肽排泄和青春期开始
  • 批准号:
    7624986
  • 财政年份:
    2008
  • 资助金额:
    $ 17.91万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政​​策的情绪动态
  • 批准号:
    10108433
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
  • 批准号:
    MR/X032809/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
  • 批准号:
    MR/X034690/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341426
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
  • 批准号:
    2341424
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Continuing Grant
Walkability and health-related quality of life in Age-Friendly Cities (AFCs) across Japan and the Asia-Pacific
日本和亚太地区老年友好城市 (AFC) 的步行适宜性和与健康相关的生活质量
  • 批准号:
    24K13490
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Discovering the (R)Evolution of EurAsian Steppe Metallurgy: Social and environmental impact of the Bronze Age steppes metal-driven economy
发现欧亚草原冶金的(R)演变:青铜时代草原金属驱动型经济的社会和环境影响
  • 批准号:
    EP/Z00022X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Research Grant
ICF: Neutrophils and cellular senescence: A vicious circle promoting age-related disease.
ICF:中性粒细胞和细胞衰老:促进与年龄相关疾病的恶性循环。
  • 批准号:
    MR/Y003365/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Research Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
  • 批准号:
    2335955
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Standard Grant
Shaping Competition in the Digital Age (SCiDA) - Principles, tools and institutions of digital regulation in the UK, Germany and the EU
塑造数字时代的竞争 (SCiDA) - 英国、德国和欧盟的数字监管原则、工具和机构
  • 批准号:
    AH/Y007549/1
  • 财政年份:
    2024
  • 资助金额:
    $ 17.91万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了