Cargando…

Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice

A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects normal development and multiple organs in adulthood. Treatment options aimed at restoring plasmalogen levels may be relevant for the therapy of peroxisomal and non-peroxisomal disorders. In this study we determined the i...

Descripción completa

Detalles Bibliográficos
Autores principales: Brites, Pedro, Ferreira, Ana Sofia, Ferreira da Silva, Tiago, Sousa, Vera F., Malheiro, Ana R., Duran, Marinus, Waterham, Hans R., Baes, Myriam, Wanders, Ronald J. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232224/
https://www.ncbi.nlm.nih.gov/pubmed/22163031
http://dx.doi.org/10.1371/journal.pone.0028539
_version_ 1782218338484617216
author Brites, Pedro
Ferreira, Ana Sofia
Ferreira da Silva, Tiago
Sousa, Vera F.
Malheiro, Ana R.
Duran, Marinus
Waterham, Hans R.
Baes, Myriam
Wanders, Ronald J. A.
author_facet Brites, Pedro
Ferreira, Ana Sofia
Ferreira da Silva, Tiago
Sousa, Vera F.
Malheiro, Ana R.
Duran, Marinus
Waterham, Hans R.
Baes, Myriam
Wanders, Ronald J. A.
author_sort Brites, Pedro
collection PubMed
description A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects normal development and multiple organs in adulthood. Treatment options aimed at restoring plasmalogen levels may be relevant for the therapy of peroxisomal and non-peroxisomal disorders. In this study we determined the in vivo efficacy of an alkyl glycerol (AG), namely, 1-O-octadecyl-rac-glycerol, as a therapeutic agent for defects in plasmalogen synthesis. To achieve this, Pex7 knockout mice, a mouse model for Rhizomelic Chondrodysplasia Punctata type 1 characterized by the absence of plasmalogens, and WT mice were fed a control diet or a diet containing 2% alkyl-glycerol. Plasmalogen levels were measured in target organs and the biochemical data were correlated with the histological analysis of affected organs. Plasmalogen levels in all peripheral tissues of Pex7 KO mice fed the AG diet for 2 months normalized to the levels of AG fed WT mice. In nervous tissues of Pex7 KO mice fed the AG-diet, plasmalogen levels were significantly increased compared to control fed KO mice. Histological analysis of target organs revealed that the AG-diet was able to stop the progression of the pathology in testis, adipose tissue and the Harderian gland. Interestingly, the latter tissues are characterized by the presence of lipid droplets which were absent or reduced in size and number when ether-phospholipids are lacking, but which can be restored with the AAG treatment. Furthermore, nerve conduction in peripheral nerves was improved. When given prior to the occurrence of major pathological changes, the AG-diet prevented or ameliorated the pathology observed in Pex7 KO mice depending on the degree of plasmalogen restoration. This study provides evidence of the beneficial effects of treating a plasmalogen deficiency with alkyl-glycerol.
format Online
Article
Text
id pubmed-3232224
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32322242011-12-09 Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice Brites, Pedro Ferreira, Ana Sofia Ferreira da Silva, Tiago Sousa, Vera F. Malheiro, Ana R. Duran, Marinus Waterham, Hans R. Baes, Myriam Wanders, Ronald J. A. PLoS One Research Article A deficiency of plasmalogens, caused by impaired peroxisomal metabolism affects normal development and multiple organs in adulthood. Treatment options aimed at restoring plasmalogen levels may be relevant for the therapy of peroxisomal and non-peroxisomal disorders. In this study we determined the in vivo efficacy of an alkyl glycerol (AG), namely, 1-O-octadecyl-rac-glycerol, as a therapeutic agent for defects in plasmalogen synthesis. To achieve this, Pex7 knockout mice, a mouse model for Rhizomelic Chondrodysplasia Punctata type 1 characterized by the absence of plasmalogens, and WT mice were fed a control diet or a diet containing 2% alkyl-glycerol. Plasmalogen levels were measured in target organs and the biochemical data were correlated with the histological analysis of affected organs. Plasmalogen levels in all peripheral tissues of Pex7 KO mice fed the AG diet for 2 months normalized to the levels of AG fed WT mice. In nervous tissues of Pex7 KO mice fed the AG-diet, plasmalogen levels were significantly increased compared to control fed KO mice. Histological analysis of target organs revealed that the AG-diet was able to stop the progression of the pathology in testis, adipose tissue and the Harderian gland. Interestingly, the latter tissues are characterized by the presence of lipid droplets which were absent or reduced in size and number when ether-phospholipids are lacking, but which can be restored with the AAG treatment. Furthermore, nerve conduction in peripheral nerves was improved. When given prior to the occurrence of major pathological changes, the AG-diet prevented or ameliorated the pathology observed in Pex7 KO mice depending on the degree of plasmalogen restoration. This study provides evidence of the beneficial effects of treating a plasmalogen deficiency with alkyl-glycerol. Public Library of Science 2011-12-06 /pmc/articles/PMC3232224/ /pubmed/22163031 http://dx.doi.org/10.1371/journal.pone.0028539 Text en Brites et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Brites, Pedro
Ferreira, Ana Sofia
Ferreira da Silva, Tiago
Sousa, Vera F.
Malheiro, Ana R.
Duran, Marinus
Waterham, Hans R.
Baes, Myriam
Wanders, Ronald J. A.
Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title_full Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title_fullStr Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title_full_unstemmed Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title_short Alkyl-Glycerol Rescues Plasmalogen Levels and Pathology of Ether-Phospholipid Deficient Mice
title_sort alkyl-glycerol rescues plasmalogen levels and pathology of ether-phospholipid deficient mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232224/
https://www.ncbi.nlm.nih.gov/pubmed/22163031
http://dx.doi.org/10.1371/journal.pone.0028539
work_keys_str_mv AT britespedro alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT ferreiraanasofia alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT ferreiradasilvatiago alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT sousaveraf alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT malheiroanar alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT duranmarinus alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT waterhamhansr alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT baesmyriam alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice
AT wandersronaldja alkylglycerolrescuesplasmalogenlevelsandpathologyofetherphospholipiddeficientmice