SPECTROSCOPIC SPECIATION OF SULFUR IN LIVING MAMMALIAN CELLS: HIV & APOPTOSIS

活哺乳动物细胞中硫的光谱形态：HIV

• 批准号: 7597956
• 负责人: GRAHAM N GEORGE
• 金额: $ 2.15万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7597956
• 关键词: Apoptosis; Area; Biochemistry; Biological; Catalysis; Cell Death; Cell Line; Cell Proliferation; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Cultured Cells; Development; Elements; Environment; Epithelial Cells; Equipment; Funding; Grant; HIV; Induction of Apoptosis; Institution; Life; Malignant Neoplasms; Mammalian Cell; Measurable; Mechanical Stimulation; Metabolism; Mitochondria; Monitor; Necrosis; Organelles; Organism; Oxidation-Reduction; Process; Research; Research Personnel; Resources; Roentgen Rays; Role; Source; Spectrum Analysis; Staging; Stimulus; Structure; Sulfur; Sulfur Metabolism Pathway; T-Lymphocyte; Techniques; Thinking; United States National Institutes of Health; absorption; accomplished suicide; human disease; immortalized cell; improved; infancy; insight; research study; response; tool

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. Sulfur is a vitally important element, with roles in structure, catalysis and metabolism in all organisms. We propose to use sulfur K-edge X-ray absorption near-edge spectroscopy to monitor and to improve our understanding of sulfur metabolism in mammalian cells, as a function of cellular development and in response to various stimuli. In particular, changes in the overall redox environment of the cell, and in organelles such as mitochondria, are thought to be important in controlling different developmental stages of the cell, from proliferation, differentiation, apoptosis and finally to necrosis. Research in this area is in its infancy, and direct information on the sulfur metabolome of the cell would be very valuable. Apoptosis, the process by which cells actively commit suicide, is very important in numerous human diseases, including HIV, where induction of apoptosis is the primary cause of T-cell death, and in cancer, where apoptosis is abnormally reduced. Apoptosis is thought to be initiated by redox changes within cells, although direct evidence for this is lacking. Such changes should be measurable by the experiments that we propose, and vital information on this important biological mechanism can anticipated. We propose to use XAS to study cultures of living mammalian cells - the MDCK immortalized cell-line, which are polarized epithelial cells. We have already developed the techniques and equipment for handling the cell cultures and recording their XAS spectra. We have also established the use of sulfur K-edge X-ray absorption near-edge spectroscopy to quantitatively speciate the sulfur in living systems. Now we plan to use these tools to study sulfur biochemistry as a function of cellular developmental status including apoptosis and during mechanical stimulation. Our experiments should provide valuable insights into the role of sulfur in these processes, and particularly in the case of apoptosis, could have important health-related ramifications.

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。 硫是一个至关重要的元素，在所有生物体中具有结构，催化和代谢中的作用。我们建议使用硫K边缘X射线吸收近边光谱法来监测和提高我们对哺乳动物细胞中硫代谢的理解，这是细胞发育的函数以及对各种刺激的反应。特别是，细胞的整体氧化还原环境以及线粒体等细胞器中的变化对于控制细胞的不同发育阶段（从增殖，分化，凋亡以及最后到坏死）很重要。该领域的研究仍处于起步阶段，有关细胞硫代谢组的直接信息将非常有价值。细胞凋亡是细胞主动自杀的过程，在包括HIV在内的许多人类疾病中非常重要，其中诱导凋亡是T细胞死亡的主要原因，在癌症中，凋亡异常降低。凋亡被认为是由细胞内的氧化还原变化引发的，尽管缺乏直接证据。我们提出的实验应该可以测量这种变化，并且可以预期有关这种重要的生物学机制的重要信息。 我们建议使用XAS研究活哺乳动物细胞的培养物 - MDCK永生的细胞系，它们是极化的上皮细胞。我们已经开发了处理细胞培养并记录其XAS光谱的技术和设备。我们还建立了使用硫K边缘X射线吸收近边光谱的使用，以定量在生物系统中规范硫。现在，我们计划使用这些工具来研究硫生物化学，这是细胞发育状态的函数，包括凋亡和机械刺激。我们的实验应提供对硫磺在这些过程中的作用的宝贵见解，尤其是在凋亡的情况下，可能具有重要的健康相关后果。