OXALINS AND CELL PROLIFERATION AND REGULATION

恶灵与细胞增殖和调节

• 批准号: 3304958
• 负责人: GORDON A HAMILTON
• 金额: $ 19.15万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3304958
• 关键词: T lymphocyte; animal tissue; biological signal transduction; cell growth regulation; cysteamine; cysteine; enzyme activity; enzyme inhibitors; flow cytometry; fluorescent dye /probe; growth media; high performance liquid chromatography; hormone regulation /control mechanism; ionophores; lectin; leukotrienes; oxalates; phorbols; prostaglandins; radioimmunoassay; tissue /cell culture

Recent investigations in our laboratory have led to the discovery that several different oxalic acid derivatives (we propose the general term 'oxalins' to refer to these compounds) are probable animal metabolites, and that they may be involved in controlling cell proliferation, in regulating metabolism, and in possibly acting as part of the intracellular messenger system for various hormones. Direct evidence has been obtained that oxalyl thiolesters (S-oxalins) and N-oxalylcysteine are indeed animal metabolites, and that S-oxalins are probably important participants in the cell proliferation process. In fact our data suggest that S-oxalins are cell proliferatIon inhibitors. If oxalins are involved in such processes, then the significance of the proposed research to human health is evident. The work would thus be relevant to physiological processes such as the uncontrolled cell proliferation encountered in cancer and the rapid cell proliferation during the immune response. Given the devastation that cancer and immune diseases can cause to humans, it seems imperative to clarify further the role of these new metabolites (especially the S- oxalins) in the response of cells to hormones, and in the regulation of cell proliferation and metabolism. That is the broad long-term objective of the proposed research. Most of the research will be performed using bovine lymph node lymphocytes. The specific aims of the proposed research are the following: (a) develop a sensitive radioimmunoassay for S-oxalins, (b) clarify further what hormones and stimulants affect the intracellular concentrations of S-oxalins, and correlate any changes with the known metabolic effects of such stimulants (among the hormones and stimulants to be investigated are: plant lectins, phorbol esters, interleukins, calcium ionophores, prostaglandins, leukotrienes, etc.), (c) Investigate the effects on the S-oxalin concentration of specific enzyme inhibitors (or activators) that are known to affect the cellular response to the foregoing hormones and stimulants, or to interfere with their production, (d) Investigate the effects that chemical removal of S-oxalins from the cells have on processes that hormones and stimulants normally affect, or on the cellular response to hormones and stimulants, (e) Investigate the effects of added S-oxalins on cellular responses to hormones, stimulants and inhibitors, and (f) determine whether S-oxalins are inhibitors or activators of key enzymes thought to be involved in the cellular response to the hormones or stimulants listed above.

我们实验室最近的研究发现 几种不同的草酸衍生物（我们提出通用术语 “恶灵”指的是这些化合物）可能是动物代谢物， 并且它们可能参与控制细胞增殖 调节新陈代谢，并可能作为细胞内的一部分 各种激素的信使系统。已获得直接证据 草酰硫醇酯（S-oxalins）和N-草酰半胱氨酸确实是动物 代谢物，并且 S-oxalins 可能是该过程的重要参与者 细胞增殖过程。事实上，我们的数据表明 S-oxalins 细胞增殖抑制剂。如果恶灵参与此类过程， 那么所提出的研究对人类健康的意义是显而易见的。 因此，这项工作将与生理过程相关，例如 癌症中遇到的不受控制的细胞增殖和快速细胞增殖 免疫反应期间的增殖。鉴于这次破坏 癌症和免疫疾病可能对人类造成，看来势在必行 进一步阐明这些新代谢物（尤其是 S- 恶灵）在细胞对激素的反应中，以及在调节 细胞增殖和代谢。这是广泛的长期目标 拟议的研究。 大部分研究将使用牛淋巴结进行 淋巴细胞。拟议研究的具体目标如下： (a) 开发一种灵敏的 S-恶灵放射免疫测定法，(b) 澄清 进一步了解哪些激素和兴奋剂影响细胞内 S-恶灵的浓度，并将任何变化与已知的相关联 此类兴奋剂（激素和兴奋剂）的代谢作用 被研究的有：植物凝集素、佛波酯、白细胞介素、钙 离子载体、前列腺素、白三烯等），(c) 研究 特定酶抑制剂（或 激活剂）已知会影响细胞对 放弃激素和兴奋剂，或干扰其产生， (d) 研究化学去除 S-oxalins 的影响 细胞具有激素和兴奋剂通常影响的过程，或 关于细胞对激素和兴奋剂的反应，(e) 研究 添加 S-oxalins 对细胞对激素、兴奋剂反应的影响 和抑制剂，并且(f)确定S-恶灵是否是抑制剂或 被认为参与细胞反应的关键酶的激活剂 上面列出的激素或兴奋剂。