Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine.

IF 6.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Antioxidants Pub Date : 2025-01-29 DOI:10.3390/antiox14020159

Alberto Ouro, Mónica Castro-Mosquera, Mariña Rodríguez-Arrizabalaga, Manuel Debasa-Mouce, Antía Custodia, Marta Aramburu-Núñez, Daniel Romaus-Sanjurjo, Josefina Casas, Isabel Lema, José Castillo, Rogelio Leira, Tomás Sobrino

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Abstract

Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide. Its activity has been associated with several molecular processes involved in migraine. Therefore, this cross-sectional study aims to study the potential role of aSMase in patients with episodic and chronic migraine. In this cross-sectional pilot study, serum samples from female healthy controls (n = 23), episodic migraine (EM) patients (n = 31), and chronic migraine (CM) patients (n = 28) were studied. The total serum levels of aSMase were determined by ELISA. In addition, the serum levels of sphingomyelin (SM), dihydro-sphingomyelin (dhSM), ceramide (Cer), and dihydro-ceramide (dhCer) were determined by mass spectrometry as biomarkers involved in the main molecular pathways associated with aSMase. aSMase serum levels were found significantly elevated in both EM (3.62 ± 1.25 ng/mL) and CM (3.07 ± 0.95 ng/mL) compared with controls (1.58 ± 0.72 ng/mL) (p < 0.0001). ROC analysis showed an area under the curve (AUC) of 0.94 (95% CI: 0.89-0.99, p < 0.0001) and 0.90 (95% CI: 0.81-0.99, p < 0.0001) for EM and CM compared to controls, respectively. Regarding other biomarkers associated with aSMase's pathways, total SM serum levels were significantly decreased in both EM (173,534 ± 39,096 pmol/mL, p < 0.01) and CM (158,459 ± 40,010 pmol/mL, p < 0.0001) compared to the control subjects (219,721 ± 36,950 pmol/mL). Elevated serum levels of aSMase were found in EM and CM patients compared to the control subjects. The decreased SM levels found in both EM and CM indicate that aSMase activity plays a role in migraine. Therefore, aSMase may constitute a new therapeutic target in migraine that should be further investigated.

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女性发作性和慢性偏头痛患者血清酸性鞘磷脂酶水平升高。

偏头痛是最常见的神经系统疾病之一，也是第二大致残的人类疾病。偏头痛的分子机制与神经肽释放、内皮功能障碍、氧化应激和炎症过程有关。酸性鞘磷脂酶（aSMase）是一种导致鞘磷脂降解产生神经酰胺的分泌酶。它的活性与偏头痛的几个分子过程有关。因此，本横断面研究旨在研究aSMase在发作性和慢性偏头痛患者中的潜在作用。在这项横断面初步研究中，研究了女性健康对照（n = 23）、发作性偏头痛（EM）患者（n = 31）和慢性偏头痛（CM）患者（n = 28）的血清样本。ELISA法检测血清总aSMase水平。此外，通过质谱法测定血清鞘磷脂（SM）、二氢鞘磷脂（dhSM）、神经酰胺（Cer）和二氢神经酰胺（dhCer）水平，作为aSMase主要相关分子途径的生物标志物。与对照组（1.58±0.72 ng/mL）相比，EM组（3.62±1.25 ng/mL）和CM组（3.07±0.95 ng/mL）血清aSMase水平均显著升高（p < 0.0001）。ROC分析显示，与对照组相比，EM和CM的曲线下面积（AUC）分别为0.94 （95% CI: 0.89-0.99, p < 0.0001）和0.90 （95% CI: 0.81-0.99, p < 0.0001）。在其他与aSMase通路相关的生物标志物方面，与对照组（219,721±36,950 pmol/mL）相比，EM组（173,534±39,096 pmol/mL, p < 0.01）和CM组（158,459±40,010 pmol/mL, p < 0.0001）血清总SM水平显著降低。与对照组相比，EM和CM患者血清aSMase水平升高。在EM和CM中发现的SM水平下降表明aSMase活性在偏头痛中起作用。因此，aSMase可能是偏头痛的一个新的治疗靶点，值得进一步研究。

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来源期刊

Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology

CiteScore

10.60

自引率

11.40%

发文量

2123

审稿时长

16.3 days

期刊介绍： Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.