Endoplasmic reticulum stress occurs in association with the extrusion of toxic extracellular vesicles from human placentae treated with antiphospholipid antibodies.
Antibodies, Antiphospholipid
/ pharmacology
Caspase 8
/ metabolism
Endoplasmic Reticulum Stress
/ drug effects
Extracellular Vesicles
/ metabolism
Female
HSP70 Heat-Shock Proteins
/ metabolism
Humans
Placenta
/ drug effects
Pre-Eclampsia
/ metabolism
Pregnancy
Pregnancy Trimester, First
Protein Kinases
/ metabolism
Tissue Culture Techniques
Trophoblasts
/ drug effects
Tumor Necrosis Factor-alpha
/ metabolism
antiphospholipid antibodies
endoplasmic reticulum stress
extracellular vesicle
placenta
preeclampsia
Journal
Clinical science (London, England : 1979)
ISSN: 1470-8736
Titre abrégé: Clin Sci (Lond)
Pays: England
ID NLM: 7905731
Informations de publication
Date de publication:
13 03 2020
13 03 2020
Historique:
received:
09
12
2019
revised:
06
02
2020
accepted:
18
02
2020
pubmed:
19
2
2020
medline:
21
7
2020
entrez:
19
2
2020
Statut:
ppublish
Résumé
Antiphospholipid autoantibodies (aPLs), a major maternal risk factor for preeclampsia, are taken into the syncytiotrophoblast where they bind intracellular vesicles and mitochondria. Subsequently, large quantities of extracellular vesicles (EVs) extruded from syncytiotrophoblast into the maternal circulation are altered such that they cause maternal endothelial cell activation. However, the mechanism driving this change is unknown. First trimester placental explants were treated with aPL for 18 h. The EVs were then collected by different centrifugation. The levels of HSP 70, misfolded proteins, caspase 8 activity, and Mixed Lineage Kinase domain-Like (MLKL) were measured in placental explants and EVs. In addition, the levels of TNF-α and CD95 in conditioned medium were also measured. Treating placental explants with aPL caused an increase in levels of HSP 70, misfolded proteins and MLKL in placental explants and EVs. Increased activity of caspase 8 was also seen in placental explants. Higher levels of TNF-α were seen conditioned medium from aPL-treated placental explant cultures. aPLs appear to induce endoplasmic reticulum stress in the syncytiotrophoblast in a manner that involved caspase 8 and TNF-α. To avoid accumulation of the associated misfolded proteins and MLKL, the syncytiotrophoblast exports these potentially dangerous proteins in EVs. It is likely that the dangerous proteins that are loaded into placental EVs in preeclampsia contribute to dysfunction of the maternal cells.
Identifiants
pubmed: 32068238
pii: 222160
doi: 10.1042/CS20191245
pmc: PMC7056451
doi:
Substances chimiques
Antibodies, Antiphospholipid
0
HSP70 Heat-Shock Proteins
0
Tumor Necrosis Factor-alpha
0
MLKL protein, human
EC 2.7.-
Protein Kinases
EC 2.7.-
Caspase 8
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
459-472Informations de copyright
© 2020 The Author(s).
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