腹腔注射的 d11-11(12)-epoxyeicosatrienoic acid 可在大鼠血浆和外周组织中迅速结合和酯化,但不会在大脑中结合和酯化

IF 3
Sho Watanabe , Felipe Da Costa Souza , Ibuki Kusumoto , Qing Shen , Nitin Nitin , Pamela J. Lein , Ameer Y. Taha
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引用次数: 0

摘要

环二十碳三烯酸(EpETrEs)是花生四烯酸细胞色素 P450 氧化的生物活性脂质介质。在体内,游离(非结合)形式的 EpETrEs 可调节多个过程,包括血流、血管生成和炎症消退。游离的 EpETrEs 被认为会通过可溶性环氧化物水解酶(sEH)迅速降解;然而,在许多组织中,大部分 EpETrEs 被酯化到复杂的脂质(如磷脂)中,这表明酯化可能在调节游离的生物活性 EpETrE 水平方面发挥着重要作用。我们通过量化雄性和雌性大鼠腹腔注射游离 d11-11(12)-Epoxyeicosatrienoic acid(d11-11(12)-EpETrE)的新陈代谢来验证这一假设。3-4 分钟后采集血浆和组织(肝脏、脂肪和大脑),检测游离和酯化脂质组分中的 d11-11(12)-EpETrE 及其 sEH 代谢物 d11-11,12-二羟基二十碳三烯酸 (d11-11,12-diHETrE)。在男性和女性体内,注射的示踪剂大部分在肝脏中回收,其次是血浆和脂肪。大脑中未检测到示踪剂,这表明大脑中的示踪剂水平是通过前体脂肪酸的内源性合成来维持的。在血浆、肝脏和脂肪中,大部分(54%)d11-11(12)-EpETrE 被酯化为磷脂或中性脂质(甘油三酯和胆固醇酯)。这项研究表明,酯化是调节体内游离 11(12)-EpETrE 水平的主要途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intraperitoneally injected d11-11(12)-epoxyeicosatrienoic acid is rapidly incorporated and esterified within rat plasma and peripheral tissues but not the brain

Epoxyeicosatrienoic acids (EpETrEs) are bioactive lipid mediators of arachidonic acid cytochrome P450 oxidation. In vivo, the free (unbound) form of EpETrEs regulate multiple processes including blood flow, angiogenesis and inflammation resolution. Free EpETrEs are thought to rapidly degrade via soluble epoxide hydrolase (sEH); yet, in many tissues, the majority of EpETrEs are esterified to complex lipids (e.g. phospholipids) suggesting that esterification may play a major role in regulating free, bioactive EpETrE levels. This hypothesis was tested by quantifying the metabolism of intraperitoneally injected free d11-11(12)-Epoxyeicosatrienoic acid (d11-11(12)-EpETrE) in male and female rats. Plasma and tissues (liver, adipose and brain) were obtained 3 to 4 min later and assayed for d11-11(12)-EpETrE and its sEH metabolite, d11-11,12-dihydroxyeicosatrienoic acid (d11-11,12-diHETrE) in both the free and esterified lipid fractions. In both males and females, the majority of injected tracer was recovered in liver followed by plasma and adipose. No tracer was detected in the brain, indicating that brain levels are maintained by endogenous synthesis from precursor fatty acids. In plasma, liver, and adipose, the majority (>54 %) of d11-11(12)-EpETrE was found esterified to phospholipids or neutral lipids (triglycerides and cholesteryl esters). sEH-derived d11-11,12-diHETrE was not detected in plasma or tissues, suggesting negligible conversion within the 3–4 min period post tracer injection. This study shows that esterification is the main pathway regulating free 11(12)-EpETrE levels in vivo.

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来源期刊
Prostaglandins, leukotrienes, and essential fatty acids
Prostaglandins, leukotrienes, and essential fatty acids Clinical Biochemistry, Endocrinology, Diabetes and Metabolism
CiteScore
5.30
自引率
0.00%
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0
审稿时长
64 days
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