OXIDATIVE DNA DAMAGE & OXYSTEROL INDUCED APOPTOSIS

DNA 氧化损伤

• 批准号: 7561498
• 负责人: SYLVETTE AYALA-TORRES
• 金额: $ 9.4万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561498
• 关键词: Apoptosis; Apoptosis Promoter; Cells; Class; Computer Retrieval of Information on Scientific Projects Database; DNA Repair; Exposure to; Foundations; Functional disorder; Funding; Generations; Genes; Grant; Human; Induction of Apoptosis; Institution; Lead; Lymphoblastic Leukemia; Lymphoid Cell; Mediating; Membrane Potentials; Mitochondria; Mitochondrial DNA; Molecular; Molecular Profiling; Nuclear; Oxidative Stress; Play; Process; Reactive Oxygen Species; Regulator Genes; Research; Research Personnel; Research Project Grants; Resistance; Resources; Role; Source; Testing; United States National Institutes of Health; apoptosis in lymphoid cells; base; cell growth; cell type; cholesterol biosynthesis; leukemia; mitochondrial dysfunction; mitochondrial membrane; repaired

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major objective of this project is to study the role of mitochondria in oxysterol-induced apoptosis of human lymphoblastic leukemia cells. Oxysterols represent a class of potent inducers of apoptosis in various cell types, particularly leukemic lymphoid cells. Oxysterols also act as powerful transcriptional regulators of genes involved in cholesterol biosynthesis, cell growth and apoptosis. Although the molecular basis of oxysterol-induced apoptosis of lymphoid cells remains unknown, some studies have suggested that oxysterol induction of apoptosis is mediated by reactive oxygen species generation. Results obtained in the previous funding cycle show that oxysterol treatment of CEM cells induces a decrease in ATP levels and loss of mitochondrial membrane potential. This project will test the hypothesis that ROS damage particularly to mitochondrial DNA plays a role in oxysterol-induced apoptosis of human leukemia cells. Our hypothesis predicts that oxidative damage to mitochondrial DNA can lead to mitochondrial dysfunction and induction of apoptosis. To test this hypothesis we will: 1) determine whether the formation and repair of oxidative damage to nuclear and mitochondrial DNA are higher in oxysterol sensitive human lymphoid cells than in oxysterol-resistant cells after exposure to oxysterols, 2) determine mitochondrial function and dysfunction in oxysterol-sensitive and resistant human lymphoid cells after exposure to oxysterols, and 3) determine the expression profile of genes involved in oxidative stress, DNA repair and apoptosis during oxysterol-induced apoptosis of lymphoid cells. This project will assist in laying the foundation for a research project directed towards the understanding of the role of mitochondria in the process of apoptosis.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的主要目的是研究线粒体在氧蛋白酶诱导的人淋巴细胞白血病细胞凋亡中的作用。 氧化酚代表了各种细胞类型（尤其是白血病淋巴样细胞）中凋亡的一类有效诱导剂。 氧蛋白酶还充当参与胆固醇生物合成，细胞生长和凋亡的强大转录调节剂。 尽管氧甲醇诱导的淋巴样细胞凋亡的分子基础尚不清楚，但一些研究表明，凋亡的氧蛋白酶诱导是由活性氧的产生介导的。 在先前的资助周期中获得的结果表明，氧蛋白酶治疗CEM细胞会诱导ATP水平降低和线粒体膜电位的损失。 该项目将检验以下假设：ROS特别对线粒体DNA的损害在氧蛋三诱导的人白血病细胞凋亡中起作用。 我们的假设预测，对线粒体DNA的氧化损伤会导致线粒体功能障碍和凋亡诱导。 为了检验这一假设，我们将：1）确定在氧蛋白酶敏感的人淋巴样细胞中对核和线粒体DNA的氧化损伤的形成和修复是否高于暴露于氧甲醇后的氧化酚耐药细胞中，2）确定在氧甲醇中，2）确定在氧化和氧化剂中的氧化和氧化物的氧化剂和脱氧于氧的氧化物均含量和抗体液的作用。在氧化应激，DNA修复和凋亡中涉及氧化应激的基因的表达谱图，在氧化酚诱导的淋巴样细胞凋亡过程中。 该项目将有助于为理解线粒体在凋亡过程中的作用的研究项目奠定基础。