Platelet mitochondrial function in health and disease

血小板线粒体在健康和疾病中的功能

基本信息

  • 批准号:
    9884665
  • 负责人:
  • 金额:
    $ 50.58万
  • 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:
    2015-04-01 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT With the increasing prevalence of obesity in the USA, diabetes mellitus is a growing concern. Most diabetic patients will die from a thrombotic vascular event (heart attack or stroke) where the effects of oxidative stress on platelets, arising from major metabolic disturbances such has hyperglycemia, play a major role. How oxidative stress directly leads to platelet dysfunction is currently an intense area of investigation. We have recently performed rigorous proteomic and metabolomic profiling in diabetic versus healthy platelets and identified specific oxidized methionine modifications in key mitochondrial metabolic proteins, that may be the source for some of the major cellular metabolic disturbances (defects in mitophagy and lipid beta- oxidation) associated with diabetic platelets. Moreover, MsrB2, an understudied mitochondrial matrix enzyme, can reverse these oxidative-stress induced methionine oxidative changes, protecting platelets. Based upon our Preliminary Studies we hypothesize that DM associated oxidative stress modifies key proteins involved in essential cellular biological and biochemical processes; mitochondria specific MsrB2 may play a critical role in reversing such potentially harmful changes, thus protecting DM patients from thrombovascular events. In addressing our hypothesis, we present three Specific Aims. Specific Aim #1 will be to assess the effects of oxidative stress on Parkin and the recently described platelet mitophagy protective process. Specific Aim #2 will be to determine whether methionine modification of HADHA, a key component of the mitochondrial trifunctional protein, perturbs mitochondrial beta-oxidation. The third Specific Aim addresses whether MsrB2 plays a role in rectifying these disturbances, in addition to possible other anti-oxidant avenues for therapy. Our team of internationally recognized experts in the areas of diabetes mellitus, platelet biology, mitochondrial biology and metabolism, will in the short term decipher important new mechanisms regulating mitochondrial dysfunction and apoptosis in diabetes mellitus. In the long term, we will have identified new targets for novel therapy against platelet mediated adverse cardiovascular events in diabetes mellitus.
项目总结/文摘

项目成果

期刊论文数量(0)
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JOHN HWA其他文献

JOHN HWA的其他文献

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{{ truncateString('JOHN HWA', 18)}}的其他基金

Platelets in vascular injury repair
血小板在血管损伤修复中的作用
  • 批准号:
    10328958
  • 财政年份:
    2020
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelets in vascular injury repair
血小板在血管损伤修复中的作用
  • 批准号:
    10560637
  • 财政年份:
    2020
  • 资助金额:
    $ 50.58万
  • 项目类别:
Yale Cooperative Center of Excellence in Hematology
耶鲁大学血液学卓越合作中心
  • 批准号:
    10677840
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet mitochondrial function in health and disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    10088457
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet Mitochondrial Function in Health and Disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    8817070
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet mitochondrial function in health and disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    10390280
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet mitochondrial function in health and disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    10600123
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet Mitochondrial Function in Health and Disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    9243286
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Platelet Mitochondrial Function in Health and Disease
血小板线粒体在健康和疾病中的功能
  • 批准号:
    9041675
  • 财政年份:
    2015
  • 资助金额:
    $ 50.58万
  • 项目类别:
Hyperglycemia, thromboxane and platelet activity in diabetes mellitus
糖尿病中的高血糖、血栓素和血小板活性
  • 批准号:
    8344530
  • 财政年份:
    2012
  • 资助金额:
    $ 50.58万
  • 项目类别:

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