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类二十烷酸在疾病的预防和治疗中的作用。

Eicosanoids in prevention and management of diseases.

机构信息

Department of Surgical Oncology, Gdynia Oncology Centre, PCK's Maritime Hospital in Gdynia, Poland.

出版信息

Curr Mol Med. 2011 Feb;11(1):13-25. doi: 10.2174/156652411794474374.

Abstract

Eicosanoids, which originate from polyunsaturated fatty acids (PUFAs), have a major impact on homeostasis maintenance as secondary signal transducers. Signal cascade, which includes reception, processing and signal transduction coming from the environment into the cell, determines the type of response evoked. Signal distortion may take place on every level of this cascade and this in consequence could lead to the development of many diseases. Any intervention into PUFAs metabolism leads to quantitative and qualitative changes of synthesized eicosanoids. Some of them promote, whereas others inhibit carcinogenesis, some are pro- or anti-inflammatory and the overall result depends on the outcome of these contradictory effects. The type and amount of produced eicosanoids depends on substrates' availability and activity of enzymes catalyzing different stages of their transformation. A particularly negative role was assigned to the over expression of phospholipase A2, cyclooxygenase-2, 5- and 12-lipoxygenases, while the contribution of other oxygenases and their metabolites is considerably less clear. The information about their interplay is extremely sparse and inadequate to understand intricacies of the mechanisms involved. There are indications that utilization of selected eicosanoids (their analogs, agonists or antagonists) could be a better way of disease prevention and treatment, more effective than excessive dietary supplementation of fatty acids. This review presents a more global picture of oxygenases and their PUFA metabolites giving a brief summary of our current understanding of perspectives and pitfalls of their regulation and mediatory action in human diseases.

摘要

类二十烷酸,源于多不饱和脂肪酸(PUFAs),作为二级信号转导物,对维持体内平衡有重大影响。信号级联反应,包括从环境到细胞的接收、处理和信号转导,决定了引发的反应类型。信号失真可能发生在这个级联反应的每一个层次上,这可能导致许多疾病的发展。任何对 PUFAs 代谢的干预都会导致合成的类二十烷酸的数量和质量发生变化。其中一些促进肿瘤发生,而另一些则抑制肿瘤发生,一些是促炎或抗炎的,总的结果取决于这些矛盾作用的结果。产生的类二十烷酸的类型和数量取决于底物的可用性和催化它们转化的不同阶段的酶的活性。磷脂酶 A2、环加氧酶-2、5-和 12-脂氧合酶的过度表达被赋予了特别负面的作用,而其他氧合酶及其代谢物的贡献则不那么明显。关于它们相互作用的信息极其稀少,不足以理解所涉及机制的复杂性。有迹象表明,利用选定的类二十烷酸(它们的类似物、激动剂或拮抗剂)可能是预防和治疗疾病的更好方法,比过度补充脂肪酸更有效。这篇综述更全面地介绍了氧合酶及其 PUFAs 代谢物,简要总结了我们目前对它们在人类疾病中的调节和介导作用的观点和陷阱的理解。

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