Mitochondrial dysfunction and biogenesis in inflammation and sepsis

炎症和脓毒症中的线粒体功能障碍和生物发生

• 批准号: 149054800
• 负责人: Dr. Christoph Schmitt
• 金额: --
• 依托单位: Wolfson Institute for Biomedical Research
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/149054800?language=en
• 关键词: Mitochondrial; dysfunction; biogenesis; inflammation; sepsis

Sepsis is a systemic inflammatory response of the body to infection and represents the major cause of death in intensive care units. Recent data identified mitochondrial damage, mediated in part by components of the immune system, as a pathologic feature of tissues during sepsis. We hypothesise that regeneration of mitochondria and restoration of oxidative phosphorylation may improve recovery from sepsis. In this project we will study mitochondrial dysfunction and biogenesis in bone marrow-derived murine macrophages upon classical activation with lipopolysaccharide and interferon-γ. Based on preliminary data we expect nitric oxide (NO), produced by inducible nitric oxide synthase, to play a critical role in both of these processes. We will employ state-of-the-art molecular biology, genetic and pharmacological tools to define the role of NO, to elucidate underlying signalling pathways and to study the consequences of mitochondrial biogenesis for macrophage survival. As an increasing number of major human pathologies are being related to chronic low-grade inflammation and mitochondrial dysfunction the proposed work has broad (patho-)physiological and clinical implications.

脓毒症是身体对感染的全身性炎症反应，是重症监护病房死亡的主要原因。最近的数据确定线粒体损伤，部分介导的免疫系统的组成部分，作为一种病理特征的组织在脓毒症。我们假设线粒体的再生和氧化磷酸化的恢复可能会改善脓毒症的恢复。在这个项目中，我们将研究骨髓来源的小鼠巨噬细胞在脂多糖和干扰素-γ经典活化后的线粒体功能障碍和生物发生。基于初步的数据，我们预计一氧化氮（NO），诱导型一氧化氮合酶产生的，在这两个过程中发挥关键作用。我们将采用最先进的分子生物学，遗传学和药理学工具来定义NO的作用，阐明潜在的信号通路，并研究线粒体生物合成对巨噬细胞存活的影响。随着越来越多的主要人类病理与慢性低度炎症和线粒体功能障碍有关，所提出的工作具有广泛的（病理）生理和临床意义。