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中文摘要
翻译
乙醇代谢产生氧化应激,慢性乙醇暴露改变 线粒体功能现存的中心问题是事件和过程之间的联系 酒精诱导的线粒体功能障碍和局部和远端组织的ROS生成 损害我们还不知道乙醇代谢是如何破坏线粒体的 和活性氧的形成,有毒物质的分子特性,也不是它们的特异性 目标的肝脏的乙醇代谢如何导致周围和远端损伤 组织也保持不透明。我们也缺乏可靠的循环标记, 组织损伤 我们最近发现了特定的氧化碎片磷脂, 转运到细胞中,在那里它们插入线粒体膜, 细胞依赖性凋亡。我们现在发现这些脂质, 介质血小板活化因子(PAF)和独特的羟基化磷脂是 在长期摄入乙醇的大鼠的循环中,所有这些都增加了。初步结果表明 这也发生在人类综合征的早期。因此这些脂质在循环中 由肝脏代谢乙醇引起的内源性氧化过程的标志物。 此外,它们本身可能通过以下方式引起近端和远端组织损伤: 它们的选择性靶点,能量线粒体的失调。 本建议的目的是:1)明确流通的来源、身份和数量 在动物和人类中循环的脂质氧化产物长期摄入乙醇。 2)确定氧化脂质如何影响线粒体功能, 线粒体功能以细胞特异性方式受损。3)确定是否 PAF乙酰水解酶,一种特异性水解氧化修饰的 磷脂,在乙醇代谢过程中保护肝细胞的线粒体功能。酒精性肝脏和组织损伤是一个重大的公共卫生问题,但足够的 累积性损害进展的标志物直到疾病晚期才可用 过程该项目将验证新的循环脂质作为疾病相关标志物, 但值得注意的是,由于这些相同的脂质会引起组织损伤,我们将能够 准确评估未来的器官损伤
英文摘要
Ethanol metabolism generates oxidative stress and chronic ethanol exposure alters mitochondrial function. The central question extant is what events and processes link alcohol-induced mitochondrial dysfunction and ROS generation to local and distal tissue damage. We do not yet know how mitochondria are damaged by ethanol metabolism and ROS formation, the molecular identity(ies) of the toxic materials, nor their specific targets. How ethanol metabolism by the liver leads to damage to surrounding and distal tissue also remains opaque. We also lack reliable circulating markers of the propensity for tissue damage. We recently identified specific oxidatively-fragmented phospholipids that are readily transported into cells, where they intercalate into mitochondrial membranes to initiate mitochondrial-dependent apoptosis. We now find these lipids, the lipid inflammatory mediator Platelet-activating Factor (PAF), and distinctive hydroxylated phospholipids are all increased in the circulation of rats chronically ingesting ethanol. Early results suggest this occurs early in the human syndrome as well. These lipids are therefore circulating markers of endogenous oxidative processes resulting from liver metabolism of ethanol. Moreover, they themselves may induce proximal and distal tissue damage through dysregulation of their selective target, energized mitochondria. The aims of this proposal are: 1) Define the source, identity, and amounts of circulating lipid oxidation products circulating in animals and human chronically ingesting ethanol. 2) Determine how oxidized lipids affect mitochondrial function, and whether mitochondrial function is compromised in a cell specific fashion. 3) Determine whether PAF acetylhydrolase, an enzyme that specifically hydrolyzes oxidatively-modified phospholipids, protects mitochondrial function of liver cells during ethanol metabolism. Alcoholic liver and tissue damage is a significant public health issue, yet adequate markers of the progression of accruing damage are not available until late in the diease process. This project will validate novel circulating lipids as disease associated markers, but, significantly, because these same lipids induce tissue damage, we will be able to accurately assess future organ damage.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
Platelet-activating factor receptor affects food intake and body weight.
血小板激活因子受体会影响食物摄入和体重。
DOI: 10.1016/j.gendis.2015.06.002
发表时间: 2015-09
期刊: Genes & diseases
影响因子: 6.8
作者: [Li W, McIntyre TM]
通讯作者: McIntyre TM
DOI: 10.1016/j.freeradbiomed.2015.05.020
发表时间: 2015-09
期刊: Free radical biology & medicine
影响因子: 7.4
作者: [Latchoumycandane C, Nagy LE, McIntyre TM]
通讯作者: McIntyre TM
Hypertension augmented COVID-19 through renin-induced internalization of platelet-ACE2 / SARS-Cov-2 complexes
  • 批准号:
    10490385
  • 项目类别:
  • 资助金额:
    $57.23万
  • 财政年份:
    2021
  • 负责人:
    Thomas M McIntyre
  • 依托单位:
Hypertension augmented COVID-19 through renin-induced internalization of platelet-ACE2 / SARS-Cov-2 complexes
  • 批准号:
    10275251
  • 项目类别:
  • 资助金额:
    $57.23万
  • 财政年份:
    2021
  • 负责人:
    Thomas M McIntyre
  • 依托单位:
Pilot Project Core
  • 批准号:
    10397511
  • 项目类别:
  • 资助金额:
    $8.96万
  • 财政年份:
    2016
  • 负责人:
    Thomas M McIntyre
  • 依托单位:
Core D: Pilot Project Core
  • 批准号:
    8977737
  • 项目类别:
  • 资助金额:
    $18.78万
  • 财政年份:
    2016
  • 负责人:
    Thomas M McIntyre
  • 依托单位:
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