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.

Authors
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
Journal
Publisher
MDPI AG
Number of issue
6
Language
English
Status
Published
Number
222
Volume
10
Year
2020
Organizations
  • 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
Keywords
COX; CYP450; Lipidomics; LOX; Oxylipins; PUFAs; Wilson’s disease
Date of creation
02.11.2020
Date of change
02.11.2020
Short link
https://repository.rudn.ru/en/records/article/record/64694/
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