OXALINS AND CELL PROLIFERATION AND REGULATION

我们实验室最近的研究发现， 几种不同的草酸衍生物（我们提出了通用术语 “类胡萝卜素”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， 调节代谢，并可能作为细胞内 各种激素的信使系统。直接证据已经获得 草酰巯基酯（S-乙二酰基）和N-草酰半胱氨酸确实是动物的 代谢物，并且S-β-内酰胺酶可能是代谢过程中的重要参与者。 细胞增殖过程。事实上，我们的数据表明，S-精氨酸是 细胞增殖抑制剂。如果这些过程中涉及到蛋白质， 那么这项研究对人类健康的重要性是显而易见的。 因此，这项工作将与生理过程有关，如 在癌症中遇到的不受控制的细胞增殖和快速细胞增殖 在免疫反应过程中增殖。考虑到 癌症和免疫疾病可能导致人类，似乎有必要 进一步阐明这些新代谢物（特别是S- 在细胞对激素的反应中， 细胞增殖和代谢。这是广泛的长期目标 的拟议研究。 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-半胱氨酸放射免疫测定法，（B）阐明 还有什么激素和兴奋剂会影响细胞内 浓度的S-甜菜碱，并与已知的任何变化相关联， 这些兴奋剂的代谢作用（在激素和兴奋剂中， 被研究的是：植物凝集素，佛波醇酯，白细胞介素，钙 离子载体、洋地黄素、白三烯等），(c)探讨 对特定酶抑制剂（或 激活剂），已知其影响细胞对 上述激素和兴奋剂，或干扰其生产， (d)调查化学去除S-草酸的影响 细胞没有激素和兴奋剂通常影响的过程，或 对激素和兴奋剂的细胞反应，（e）调查 添加的S-甜菜碱对细胞对激素、兴奋剂 和抑制剂，和（f）确定S-精氨酸是否是抑制剂或 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。

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.