Exogenous oxygen is required for prostanoid induction under brain ischemia as evidence for a novel regulatory mechanism.
Exogenous oxygen is required for prostanoid induction under brain ischemia as evidence for a novel regulatory mechanism.
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DOI：
10.1016/j.jlr.2023.100452
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发表时间：
2023-11
影响因子：
6.5
通讯作者：
Golovko, Mikhail Y.
中科院分区：
文献类型：
--
作者：
Seeger, Drew R.;Schofield, Brennon;Besch, Derek;Golovko, Svetlana A.;Kotha, Peddanna;Parmer, Meredith;Solaymani-Mohammadi, Shahram;Golovko, Mikhail Y.
关键词：
以前，我们和其他人报道了脑内前列腺素(PG)的快速和戏剧性的增加，包括前列腺素、前列腺素和血栓素，传统上解释这是通过磷脂酶作为环氧合酶(COX)的底物激活酯化的花生四烯酸(20：4N6)释放的。然而，在这个机制中，另一种所需的COX底物氧气的可用性没有被考虑到。为了探讨这一通过氧供应上调PG的机制，我们在开颅手术前使用头部聚焦微波辐射(MW)原位灭活酶，分析了小鼠脑PG、游离20：4N6和脑缺血后不同时间点的氧水平。S脑缺血时氧半衰期为5.32±0.45，12小时内降至检测不到的水平，而S脑缺血30小时时未见明显的游离20：4N6或Pg变化。此外，与基础值相比，缺血后2min和10min的PG无明显升高，而游离20：4N6分别使∼50和∼增加100倍。然而，当缺血后开颅手术为活性酶提供氧气的非MW组织时，PG使∼增加了30倍。此外，在无MW的缺氧条件下进行的开颅手术不会导致PG的诱导，而将这些脑暴露于大气中的氧气可以显著地诱导PG。我们的结果首次表明，在缺血情况下，氧气供应是PG产生的另一个重要调节因素。需要进一步的研究来探讨COX/PG通过组织氧浓度调节的生理作用。
Previously, we and others reported a rapid and dramatic increase in brain prostanoids (PG), including prostaglandins, prostacyclins, and thromboxanes, under ischemia that is traditionally explained through the activation of esterified arachidonic acid (20:4n6) release by phospholipases as a substrate for cyclooxygenases (COX). However, the availability of another required COX substrate, oxygen, has not been considered in this mechanism. To address this mechanism for PG upregulation through oxygen availability, we analyzed mouse brain PG, free 20:4n6, and oxygen levels at different time points after ischemic onset using head-focused microwave irradiation (MW) to inactivate enzymes in situ before craniotomy. The oxygen half-life in the ischemic brain was 5.32 ± 0.45 s and dropped to undetectable levels within 12 s of ischemia onset, while there were no significant free 20:4n6 or PG changes at 30 s of ischemia. Furthermore, there was no significant PG increase at 2 and 10 min after ischemia onset compared to basal levels, while free 20:4n6 was increased ∼50 and ∼100 fold, respectively. However, PG increased ∼30-fold when ischemia was followed by craniotomy of nonMW tissue that provided oxygen for active enzymes. Moreover, craniotomy performed under anoxic conditions without MW did not result in PG induction, while exposure of these brains to atmospheric oxygen significantly induced PG. Our results indicate, for the first time, that oxygen availability is another important regulatory factor for PG production under ischemia. Further studies are required to investigate the physiological role of COX/PG regulation through tissue oxygen concentration.
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影响因子：
2.9
作者：
ANTON, RF;WALLIS, C;RANDALL, CL
通讯作者：
RANDALL, CL
影响因子：
1.9
作者：
Golovko SA;Golovko MY
通讯作者：
Golovko MY
DOI：
10.1073/pnas.1107533108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Clasadonte, Jerome;Poulain, Pierre;Prevot, Vincent
通讯作者：
Prevot, Vincent
DOI：
10.1016/s0034-5687(01)00306-1
发表时间：
2001-11-15
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Erecinska, M;Silver, IA
通讯作者：
Silver, IA
影响因子：
1.9
作者：
Brose SA;Baker AG;Golovko MY
通讯作者：
Golovko MY