Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid.
Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid.
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DOI：
10.1016/j.bbalip.2014.10.008
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Rokach J
中科院分区：
文献类型：
--
作者：
Powell WS;Rokach J
花生四烯酸可以被多种不同的酶氧化，包括脂氧合酶、环加氧酶和细胞色素P450，并且可以由于脂质过氧化而转化为氧化产物的复杂混合物。这些反应中的初始产物是氢过氧二十碳四烯酸（HpETE）和羟基二十碳四烯酸（HETE）。氧代二十碳四烯酸（oxo-ETEs）可以通过各种脱氢酶对HETEs的作用或通过HpETEs的脱水形成。虽然大量不同的HETE和oxo-ETE已被确定，这篇评论将主要集中在5-oxo-ETE，5S-HETE，12 S-HETE和15 S-HETE。其他相关的花生四烯酸代谢物也将讨论较少的细节。5-氧代-ETE是通过选择性酶5-羟基类二十烷酸脱氢酶氧化5-脂氧合酶产物5S-HETE合成的。它的作用是由选择性OXE受体介导的，该受体在嗜酸性粒细胞上高度表达，这表明它可能在嗜酸性粒细胞疾病如哮喘中很重要。5-氧代-ETE似乎也刺激肿瘤细胞增殖，也可能参与癌症。高选择性和有效的OXE受体拮抗剂最近已成为可用的，并可能有助于澄清其病理生理作用。12-脂氧合酶产物12 S-HETE通过GPR 31受体起作用并促进肿瘤细胞增殖和转移，因此可能是癌症治疗中有希望的靶点。它也可能作为促炎介质参与糖尿病。相反，15 S-HETE可能对癌症有保护作用。除了GPCR，更高浓度的HETE和oxo-ETE可以激活过氧化物酶体增殖物激活受体（PPARs），并可能通过这种机制调节各种过程。
Arachidonic acid can be oxygenated by a variety of different enzymes, including lipoxygenases, cyclooxygenases, and cytochrome P450s, and can be converted to a complex mixture of oxygenated products as a result of lipid peroxidation. The initial products in these reactions are hydroperoxyeicosatetraenoic acids (HpETEs) and hydroxyeicosatetraenoic acids (HETEs). Oxoeicosatetraenoic acids (oxo-ETEs) can be formed by the actions of various dehydrogenases on HETEs or by dehydration of HpETEs. Although a large number of different HETEs and oxo-ETEs have been identified, this review will focus principally on 5-oxo-ETE, 5S-HETE, 12S-HETE, and 15S-HETE. Other related arachidonic acid metabolites will also be discussed in less detail. 5-Oxo-ETE is synthesized by oxidation of the 5-lipoxygenase product 5S-HETE by the selective enzyme, 5-hydroxyeicosanoid dehydrogenase. It actions are mediated by the selective OXE receptor, which is highly expressed on eosinophils, suggesting that it may be important in eosinophilic diseases such as asthma. 5-Oxo-ETE also appears to stimulate tumor cell proliferation and may also be involved in cancer. Highly selective and potent OXE receptor antagonists have recently become available and could help to clarify its pathophysiological role. The 12-lipoxygenase product 12S-HETE acts by the GPR31 receptor and promotes tumor cell proliferation and metastasis and could therefore be a promising target in cancer therapy. It may also be involved as a proinflammatory mediator in diabetes. In contrast, 15S-HETE may have a protective effect in cancer. In addition to GPCRs, higher concentration of HETEs and oxo-ETEs can activate peroxisome proliferator-activated receptors (PPARs) and could potentially regulate a variety of processes by this mechanism.
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DOI：
10.1016/j.bbalip.2010.08.002
发表时间：
2010-12
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Bannenberg G;Serhan CN
通讯作者：
Serhan CN
影响因子：
3.9
作者：
Bronstein, JC;Bull, AW
通讯作者：
Bull, AW
影响因子：
3
作者：
Campbell WB;Gauthier KM
通讯作者：
Gauthier KM
DOI：
10.1007/bf01966527
发表时间：
1987-08-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
AGINS, AP;ZIPKIN, RE;TAFFER, IM
通讯作者：
TAFFER, IM
影响因子：
3.9
作者：
BRASH, AR;BOEGLIN, WE;BLAIR, IA
通讯作者：
BLAIR, IA