The role of distinctive sphingolipids in the inflammatory and apoptotic effects of electronegative LDL on monocytes
Puig Grifol, Núria (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Estruch, Montserrat (Institut d'Investigació Biomèdica Sant Pau)
Jin, Lei (Institut d'Investigació Biomèdica Sant Pau)
Sanchez-Quesada, Jose Luis (Institut d'Investigació Biomèdica Sant Pau)
Benitez, Sonia (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	Electronegative low-density lipoprotein (LDL(−)) is a minor LDL subfraction that is present in blood with inflammatory and apoptotic effects. We aimed to evaluate the role of sphingolipids ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) in the LDL(−)-induced effect on monocytes. Total LDL was subfractioned into native LDL and LDL(−) by anion-exchange chromatography and their sphingolipid content evaluated by mass spectrometry. LDL subfractions were incubated with monocytes in the presence or absence of enzyme inhibitors: chlorpromazine (CPZ), D-erythro-2-(N-myristoyl amino)-1-phenyl-1-propanol (MAPP), and N,N-dimethylsphingosine (DMS), which inhibit Cer, Sph, and S1P generation, respectively. After incubation, we evaluated cytokine release by enzyme-linked immunosorbent assay (ELISA) and apoptosis by flow cytometry. LDL(−) had an increased content in Cer and Sph compared to LDL(+). LDL(−)-induced cytokine release from cultured monocytes was inhibited by CPZ and MAPP, whereas DMS had no effect. LDL(−) promoted monocyte apoptosis, which was inhibited by CPZ, but increased with the addition of DMS. LDL enriched with Sph increased cytokine release in monocytes, and when enriched with Cer, reproduced both the apoptotic and inflammatory effects of LDL(−). These observations indicate that Cer content contributes to the inflammatory and apoptotic effects of LDL(−) on monocytes, whereas Sph plays a more important role in LDL(−)-induced inflammation, and S1P counteracts apoptosis.
Grants:	Instituto de Salud Carlos III FIS/PI13/00364 Instituto de Salud Carlos III FIS/PI16/00471 Instituto de Salud Carlos III CIBERDEM/CB07/08/0016 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-1149
Note:	Altres ajuts: Fundació La Marató de TV3: 158/U/2017
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:	Electronegative LDL ; Ceramide ; Sphingosine ; Inflammation ; Apoptosis ; Monocytes
Published in:	Biomolecules, Vol. 9 Núm. 8 (august 2019) , p. 300, ISSN 2218-273X

DOI: 10.3390/biom9080300
PMID: 31344975

14 p, 2.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles