Myeloperoxidase and Septic Conditions Disrupt Sphingolipid Homeostasis in Murine Brain Capillaries In Vivo and Immortalized Human Brain Endothelial Cells In Vitro.
blood–brain barrier
calorimetry
ceramides
cytokines
fatty acid
mitochondrial function
myeloperoxidase
sphingomyelins
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
09 Feb 2020
09 Feb 2020
Historique:
received:
12
12
2019
revised:
27
01
2020
accepted:
06
02
2020
entrez:
14
2
2020
pubmed:
14
2
2020
medline:
21
11
2020
Statut:
epublish
Résumé
During inflammation, activated leukocytes release cytotoxic mediators that compromise blood-brain barrier (BBB) function. Under inflammatory conditions, myeloperoxidase (MPO) is critically involved in inflicting BBB damage. We used genetic and pharmacological approaches to investigate whether MPO induces aberrant lipid homeostasis at the BBB in a murine endotoxemia model. To corroborate findings in a human system we studied the impact of sera from sepsis and non-sepsis patients on brain endothelial cells (hCMEC/D3). In response to endotoxin, the fatty acid, ceramide, and sphingomyelin content of isolated mouse brain capillaries dropped and barrier dysfunction occurred. In mice, genetic deficiency or pharmacological inhibition of MPO abolished these alterations. Studies in metabolic cages revealed increased physical activity and less pronounced sickness behavior of MPO
Identifiants
pubmed: 32050431
pii: ijms21031143
doi: 10.3390/ijms21031143
pmc: PMC7037060
pii:
doi:
Substances chimiques
Sphingolipids
0
Peroxidase
EC 1.11.1.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : J 4205
Pays : Austria
Organisme : Austrian Science Fund
ID : MOLIN-W1241, P30882, J4205-B27
Organisme : Franz Lanyar Stiftung
ID : 411
Organisme : Oesterreichische Nationalbank
ID : 17600
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