Cargando…

Distinctive sphingolipid patterns in chronic multiple sclerosis lesions

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms...

Descripción completa

Detalles Bibliográficos
Autores principales: Podbielska, Maria, Szulc, Zdzislaw M., Ariga, Toshio, Pokryszko-Dragan, Anna, Fortuna, Wojciech, Bilinska, Małgorzata, Podemski, Ryszard, Jaskiewicz, Ewa, Kurowska, Ewa, Yu, Robert K., Hogan, Edward L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604719/
https://www.ncbi.nlm.nih.gov/pubmed/32769146
http://dx.doi.org/10.1194/jlr.RA120001022
_version_ 1783604190540464128
author Podbielska, Maria
Szulc, Zdzislaw M.
Ariga, Toshio
Pokryszko-Dragan, Anna
Fortuna, Wojciech
Bilinska, Małgorzata
Podemski, Ryszard
Jaskiewicz, Ewa
Kurowska, Ewa
Yu, Robert K.
Hogan, Edward L.
author_facet Podbielska, Maria
Szulc, Zdzislaw M.
Ariga, Toshio
Pokryszko-Dragan, Anna
Fortuna, Wojciech
Bilinska, Małgorzata
Podemski, Ryszard
Jaskiewicz, Ewa
Kurowska, Ewa
Yu, Robert K.
Hogan, Edward L.
author_sort Podbielska, Maria
collection PubMed
description Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease.
format Online
Article
Text
id pubmed-7604719
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher The American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-76047192020-11-04 Distinctive sphingolipid patterns in chronic multiple sclerosis lesions Podbielska, Maria Szulc, Zdzislaw M. Ariga, Toshio Pokryszko-Dragan, Anna Fortuna, Wojciech Bilinska, Małgorzata Podemski, Ryszard Jaskiewicz, Ewa Kurowska, Ewa Yu, Robert K. Hogan, Edward L. J Lipid Res Research Articles Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease. The American Society for Biochemistry and Molecular Biology 2020-11 2020-08-07 /pmc/articles/PMC7604719/ /pubmed/32769146 http://dx.doi.org/10.1194/jlr.RA120001022 Text en Copyright © 2020 Podbielska et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. http://creativecommons.org/licenses/by/4.0/ Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license.
spellingShingle Research Articles
Podbielska, Maria
Szulc, Zdzislaw M.
Ariga, Toshio
Pokryszko-Dragan, Anna
Fortuna, Wojciech
Bilinska, Małgorzata
Podemski, Ryszard
Jaskiewicz, Ewa
Kurowska, Ewa
Yu, Robert K.
Hogan, Edward L.
Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title_full Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title_fullStr Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title_full_unstemmed Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title_short Distinctive sphingolipid patterns in chronic multiple sclerosis lesions
title_sort distinctive sphingolipid patterns in chronic multiple sclerosis lesions
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604719/
https://www.ncbi.nlm.nih.gov/pubmed/32769146
http://dx.doi.org/10.1194/jlr.RA120001022
work_keys_str_mv AT podbielskamaria distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT szulczdzislawm distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT arigatoshio distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT pokryszkodragananna distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT fortunawojciech distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT bilinskamałgorzata distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT podemskiryszard distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT jaskiewiczewa distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT kurowskaewa distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT yurobertk distinctivesphingolipidpatternsinchronicmultiplesclerosislesions
AT hoganedwardl distinctivesphingolipidpatternsinchronicmultiplesclerosislesions