Kytikova O Yu, Kovalenko I S, Novgorodtseva T P, Denisenko Yu K
Vladivostok Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration-Institute of Medical Climatology and Rehabilitative Treatment, Vladivostok, Russia.
Dokl Biochem Biophys. 2024 Dec;519(1):512-520. doi: 10.1134/S1607672924701126. Epub 2024 Sep 16.
Hydroperoxyeicosatetraenoic acids (HETEs) are metabolites of arachidonic acid that are oxidized by a family of enzymes including cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. These enzymes are widely present in various organs and tissues, and the HETEs they synthesize perform an important function in the regulation of immune reactions and haemostasis processes under physiological and pathophysiological conditions. More researchers confirm the role of these oxidized metabolites in modulating inflammation in asthma. The high production of HETEs in allergic and severe asthma indicates their involvement in the processes of an acute inflammatory response. On the other hand, disturbance of the metabolic transformation of arachidonic acid contributes to the development of chronic inflammation due to insufficient synthesis of mediators that resolve inflammatory processes. Several HETEs have both pro-inflammatory and anti-inflammatory effects, which underscores the ongoing interest in their involvement in the pathogenesis of asthma. At the same time, research results are scarce. Based on an analysis of the literature, the pathways of metabolic transformation of 5-HETE, 12-HETE, and 15-HETE with the participation of cyclooxygenases, lipoxygenases, and cytochrome P-450, as well as their role in asthma pathogenesis, were discussed. The PubMed database was searched for information covering the last five years using selected inclusion criteria. Information queries included the following set of keywords: "bronchial asthma, hydroxyeicosatetraenoic acids, 5-HETE, 12-HETE, 15-HETE." Literature data indicate that the role of HETEs in human physiology and pathology, including the modulation of inflammation in asthma, requires comprehensive study to selectively modulate the enzymatic pathways of arachidonic acid metabolism leading to the production of these mediators.
氢过氧化二十碳四烯酸（HETEs）是花生四烯酸的代谢产物，可被包括环氧化酶、脂氧合酶和细胞色素P450酶在内的一系列酶氧化。这些酶广泛存在于各种器官和组织中，它们合成的HETEs在生理和病理生理条件下的免疫反应调节和止血过程中发挥重要作用。越来越多的研究人员证实了这些氧化代谢产物在调节哮喘炎症中的作用。在过敏性和重度哮喘中HETEs的高生成表明它们参与了急性炎症反应过程。另一方面，由于解决炎症过程的介质合成不足，花生四烯酸代谢转化的紊乱导致慢性炎症的发展。几种HETEs具有促炎和抗炎作用，这突出了人们对它们参与哮喘发病机制的持续关注。同时，研究结果很少。基于文献分析，讨论了5-HETE、12-HETE和15-HETE在环氧化酶、脂氧合酶和细胞色素P-450参与下的代谢转化途径，以及它们在哮喘发病机制中的作用。使用选定的纳入标准在PubMed数据库中搜索了过去五年的信息。信息查询包括以下一组关键词：“支气管哮喘、羟基二十碳四烯酸、5-HETE、12-HETE、15-HETE”。文献数据表明，HETEs在人体生理和病理中的作用，包括对哮喘炎症的调节，需要进行全面研究，以选择性地调节花生四烯酸代谢的酶促途径，从而产生这些介质。
