Oxylipin profiles in plasma of patients with wilson’s disease

Wilson’s disease (WD) is a rare autosomal recessive metabolic disorder resulting from mutations in the copper-transporting, P-type ATPase gene ATP7B gene, but influences of epigenetics, environment, age, and sex-related factors on the WD phenotype complicate diagnosis and clinical manifestations. Oxylipins, derivatives of omega-3, and omega-6 polyunsaturated fatty acids (PUFAs) are signaling mediators that are deeply involved in innate immunity responses; the regulation of inflammatory responses, including acute and chronic inflammation; and other disturbances related to any system diseases. Therefore, oxylipin profile tests are attractive for the diagnosis of WD. With UPLC-MS/MS lipidomics analysis, we detected 43 oxylipins in the plasma profiles of 39 patients with various clinical manifestations of WD compared with 16 healthy controls (HCs). Analyzing the similarity matrix of oxylipin profiles allowed us to cluster patients into three groups. Analysis of the data by VolcanoPlot and partial least square discriminant analysis (PLS-DA) showed that eight oxylipins and lipids stand for the variance between WD and HCs: eicosapentaenoic acid EPA, oleoylethanolamide OEA, octadecadienoic acids 9-HODE, 9-KODE, 12-hydroxyheptadecatrenoic acid 12-HHT, prostaglandins PGD2, PGE2, and 14,15-dihydroxyeicosatrienoic acids 14,15-DHET. The compounds indicate the involvement of oxidative stress damage, inflammatory processes, and peroxisome proliferator-activated receptor (PPAR) signaling pathways in this disease. The data reveal novel possible therapeutic targets and intervention strategies for treating WD. © 2020 by the authors.

Авторы
Azbukina N.V.1 , Lopachev A.V. 2 , Chistyakov D.V. 3 , Goriainov S.V. 4 , Astakhova A.A.3 , Poleshuk V.V.5 , Kazanskaya R.B.6 , Fedorova T.N. 2 , Sergeeva M.G. 3
Журнал
Издательство
MDPI AG
Номер выпуска
6
Язык
Английский
Статус
Опубликовано
Номер
222
Том
10
Год
2020
Организации
  • 1 Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Moscow, 119234, Russian Federation
  • 2 Laboratory of Clinical and Experimental neurochemistry, Research Center of Neurology, Moscow, 125367, Russian Federation
  • 3 Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russian Federation
  • 4 SREC PFUR Peoples’ Friendship University of Russia, RUDN University, Moscow, 117198, Russian Federation
  • 5 Research Center of Neurology, Moscow, 125367, Russian Federation
  • 6 Biological Department, Saint Petersburg State University, Universitetskaya Emb. 7/9, St Petersburg, 199034, Russian Federation
Ключевые слова
COX; CYP450; Lipidomics; LOX; Oxylipins; PUFAs; Wilson’s disease
Дата создания
02.11.2020
Дата изменения
02.11.2020
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/64694/
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