Involvement of free radical-mediated oxidation in the pathogenesis of pseudoexfoliation syndrome detected based on specific hydroxylinoleate isomers
Involvement of free radical-mediated oxidation in the pathogenesis of pseudoexfoliation syndrome detected based on specific hydroxylinoleate isomers
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DOI：
10.1016/j.freeradbiomed.2019.12.011
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发表时间：
2020-02-01
影响因子：
7.4
通讯作者：
Yoshida, Yasukazu
中科院分区：
文献类型：
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作者：
Umeno, Aya;Tanito, Masaki;Yoshida, Yasukazu
我们之前报道过，根据还原和皂化后羟亚油酸（HODE）和羟基花生四烯酸（HETE）异构体血清水平的测量，酶促和单线态氧介导的脂肪酸氧化可能是原发性开角型青光眼受试者的主要氧化途径。在本研究中，我们测量了 HODE 和 HETE 异构体的血清水平，以研究剥脱综合征 (EX) 的发病机制。本研究总共纳入了 311 名日本受试者，其中包括 EX 患者 (n = 192) 和非青光眼对照受试者 (n = 119)。 EX患者（n = 192）根据眼压分为EX伴青光眼（EXG）组和EX不伴青光眼（EXS）组（分别为n = 128和n = 64）。 EX组的总HODE（/亚油酸）血清水平（202.7+/-153.2μmol/mol）显着（p=0.0426）高于对照组（167.1+/-105.3μmol/mol）。在 HODE 异构体中，EX 和 EXG 组中自由基介导的氧化产物 9-(E,E)-HODE (p < 0.0001) 和 13-(E,E)-HODE (p < 0.0001) 水平高于对照组，而 EXS 和对照组之间没有观察到显着差异。在调整人口统计参数的差异后，多变量分析证实了 9- 和 13-(E,E)-HODE 与 EX 之间的关联。这是与 EX 发病机制相关的自由基介导的氧化产物急剧增加的第一份报告，我们的研究结果表明自由基介导的氧化可能是 EX 恶化的原因之一。
We reported previously that enzymatic and singlet oxygen-mediated fatty acid oxidation may be major oxidation pathways in subjects with primary open angle glaucoma, based on measurement of serum levels of hydroxylinoleate (HODE) and hydroxyarachidonate (HETE) isomers after reduction and saponification. In this study, we measured serum levels of HODE and HETE isomers to investigate the pathogenesis of exfoliation syndrome (EX). In total, 311 Japanese subjects comprising EX patients (n = 192) and non-glaucomatous control subjects (n = 119) were included in this study. Patients with EX (n = 192) were divided into EX with glaucoma (EXG) and EX without glaucoma (EXS) groups (n = 128 and n = 64, respectively) depending on the intraocular pressure. Total HODE (/linoleic acid) serum levels were significantly (p = 0.0426) higher in the EX group (202.7 +/- 153.2 mu mol/mol) than in the controls (167.1 +/- 105.3 mu mol/mol). Among the HODE isomers, the levels of 9-(E,E)-HODEs (p < 0.0001) and 13-(E,E)-HODEs (p < 0.0001), both free radical-mediated oxidation products, were higher in the EX and EXG groups than in the controls, whereas no significant difference was observed between EXS and controls. After adjusting for differences in demographic parameters, multivariate analyses confirmed the association between 9- and 13-(E,E)-HODEs and EX. This is the first report of a dramatic increase in free radical-mediated oxidation products related to the pathogenesis of EX, and our findings suggest that free radical-mediated oxidation can be one of the causes of deterioration in EX.