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发现的结构。线粒体的主要功能是将能量转换为可由细胞使用的形式。该单元使用这种能量来执行生存和功能所需的特定工作。此外，线粒体在启动引发导致细胞死亡的事件的信号中起着至关重要的作用。因此，线粒体是调节细胞死亡和存活的细胞的关键组成细胞器。这些动态细胞器会经历连续的伸长和碎片化过程，以保持适当的功能并满足细胞需求。遗传异常，疾病或毒性引起的这些过程的重大破坏会影响细胞的能量产生。这会导致细胞功能障碍和死亡。蛛网膜酸（AA）是在细胞膜中发现的分子，可以响应几种刺激（例如激素和细胞应激）而释放。细胞中的蛋白质将其分解为活性分子，称为环氧树钠酸（EET）和羟基羟基乙烯烯酸（HETE），它们可以调节体内各种功能。最近的研究表明，EET和HETE具有竞争作用，EET促进细胞存活并促进细胞死亡。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。当前的赠款提案调查了Eets和Hetes如何调节线粒体功能和能源生产。这项研究的结果将确定新的调节机制，并提高我们对线粒体功能的理解。