Cytochrome P450 Derived Metabolites of Arachidonic Acid Differentially Regulate Cell Death Pathways

细胞色素 P450 衍生的花生四烯酸代谢物差异调节细胞死亡途径

• 批准号: 386091-2013
• 负责人: Seubert, John
• 金额: $ 2.19万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528735
• 关键词: Cytochrome; P450; Derived; Metabolites; Arachidonic

Mitochondria are structures that are found in virtually every cell. The main function of mitochondria is to convert energy into forms that are usable by the cell. The cell uses this energy to perform the specific work necessary for survival and function. In addition, mitochondria play a vital role in initiating signals that trigger events leading to cell death. Therefore, mitochondria are key components organelles) of cells that regulate both cell death and survival. These dynamic organelles undergo continuous elongation and fragmentation processes to maintain proper function and meet cellular demands. Significant disruption in these processes caused by genetic abnormalities, disease or toxicity can impact the energy production of the cell. This can result in cellular dysfunction and death. Arachidonic acid (AA) is a molecule found in cell membranes that can be released in response to several stimuli such as hormones and cellular stress. Proteins within a cell break it down into active molecules called epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETE), which can regulate various functions in the body. Recent research has demonstrated that EETs and HETEs have competing effects, where EETs promote cell survival and HETE promote cell death. My long-term research program objectives are to understand how these molecules regulate mitochondrial function and limit injury. The current grant proposal investigates how EETs and HETEs regulate mitochondrial function and energy production. Results from this study will identify new regulatory mechanisms and advance our understanding of mitochondrial function.

线粒体是几乎每个细胞中都存在的结构。线粒体的主要功能是将能量转化为细胞可用的形式。细胞利用这种能量来执行生存和功能所需的特定工作。此外，线粒体在引发导致细胞死亡的事件的信号启动方面发挥着至关重要的作用。因此，线粒体是调节细胞死亡和存活的细胞的关键组成部分。这些动态细胞器经历持续的伸长和破碎过程，以维持正常的功能并满足细胞的需求。遗传异常、疾病或毒性引起的这些过程的严重破坏可能会影响细胞的能量产生。这可能导致细胞功能障碍和死亡。花生四烯酸 (AA) 是一种存在于细胞膜中的分子，可以响应激素和细胞应激等多种刺激而释放。细胞内的蛋白质将其分解为称为环氧二十碳三烯酸 (EET) 和羟基二十碳四烯酸 (HETE) 的活性分子，它们可以调节体内的各种功能。最近的研究表明，EET 和 HETE 具有竞争作用，其中 EET 促进细胞存活，HETE 促进细胞死亡。我的长期研究计划目标是了解这些分子如何调节线粒体功能并限制损伤。当前的拨款提案研究了 EET 和 HETE 如何调节线粒体功能和能量产生。这项研究的结果将确定新的调控机制并增进我们对线粒体功能的理解。