Oxylipin Profiles in Plasma of Patients with Wilson’s Disease

Metabolites

卷:10

AlinaA. Astakhova¹  DmitryV. Chistyakov¹  MarinaG. Sergeeva¹  RognedaB. Kazanskaya²  NadezhdaV. Azbukina³  TatianaN. Fedorova⁴  AlexanderV. Lopachev⁴  VsevolodV. Poleshuk⁵  SergeiV. Goriainov⁶ 

[1] Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia;

[2] Biological Department, Saint Petersburg State University, Universitetskaya Emb. 7/9, St Petersburg 199034, Russia;

[3] Faculty of Bioengineering and Bioinformatics, Moscow Lomonosov State University, Moscow 119234, Russia;

[4] Laboratory of Clinical and Experimental neurochemistry, Research Center of Neurology, Moscow 125367, Russia;

[5] Research Center of Neurology, Moscow 125367, Russia;

[6] SREC PFUR Peoples’ Friendship University of Russia (RUDN University), Moscow 117198, Russia;

关键词: COX;    CYP450;    LOX;    oxylipins;    PUFAs;    lipidomics;   

DOI  :  10.3390/metabo10060222

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown