HPLC-MS/MS Oxylipin Analysis of Plasma from Amyotrophic Lateral Sclerosis Patients
Mastrogiovanni, Mauricio (Universidad de la República, Montevideo. Departamento de Bioquímica)
Trostchansky, Andrés (Universidad de la República, Montevideo. Departamento de Bioquímica)
Naya, Hugo (Institut Pasteur-Montevideo. Unidad de Bioinformática)
Dominguez, Raúl (Institut d'Investigació Biomèdica de Bellvitge)
Marco, Carla (Institut d'Investigació Biomèdica de Bellvitge)
Povedano, Mònica (Institut d'Investigació Biomèdica de Bellvitge)
López Vales, Rubén (Universitat Autònoma de Barcelona. Institut de Neurociències)
Rubbo, Homero (Universidad de la República, Montevideo. Departamento de Bioquímica)

Date:	2022
Abstract:	Oxylipins play a critical role in regulating the onset and resolution phase of inflammation. Despite inflammation is a pathological hallmark in amyotrophic lateral sclerosis (ALS), the plasma oxylipin profile of ALS patients has not been assessed yet. Herein, we develop an oxylipin profile-targeted analysis of plasma from 74 ALS patients and controls. We found a significant decrease in linoleic acid-derived oxylipins in ALS patients, including 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE. These derivatives have been reported as important regulators of inflammation on different cell systems. In addition, some 5-lipoxygenase metabolites, such as 5-hydroxy- eicosatetraenoic acid also showed a significant decrease in ALS plasma samples. Isoprostanes of the F2α family were detected only in ALS patients but not in control samples, while the hydroxylated metabolite 11-HETE significantly decreased. Despite our effort to analyze specialized pro-resolving mediators, they were not detected in plasma samples. However, we found the levels of 14-hydroxy-docosahexaenoic acid, a marker pathway of the Maresin biosynthesis, were also reduced in ALS patients, suggesting a defective activation in the resolution programs of inflammation in ALS. We further analyze oxylipin concentration levels in plasma from ALS patients to detect correlations between these metabolites and some clinical parameters. Interestingly, we found that plasmatic levels of 13-HODE and 9-HODE positively correlate with disease duration, expressed as days since onset. In summary, we developed a method to analyze "(oxy)lipidomics" in ALS human plasma and found new profiles of metabolites and novel lipid derivatives with unknown biological activities as potential footprints of disease onset.
Grants:	Agencia Estatal de Investigación PID2020-120267RB-I00 Ministerio de Sanidad y Consumo CB06/05/1105 "la Caixa" Foundation 100010434
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Amyotrophic lateral sclerosis ; Lipidomics ; Oxylipin ; Specialized pro-resolving mediators ; Mass spectrometry
Published in:	Biomedicines, Vol. 10 Núm. 3 (2022) , p. 674, ISSN 2227-9059

DOI: 10.3390/biomedicines10030674
PMID: 35327476

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