原创力文档cross-talk between oxysterols and glucocorticoids differential regulation of secreted phopholipase a2 and impact on oligodendrocyte death相声oxysterols与糖皮质激素分泌微分调节phopholipase a2和对少突细胞死亡的影响.pdfVIP
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cross-talk between oxysterols and glucocorticoids differential regulation of secreted phopholipase a2 and impact on oligodendrocyte death相声oxysterols与糖皮质激素分泌微分调节phopholipase a2和对少突细胞死亡的影响
Cross-Talk between Oxysterols and Glucocorticoids:
Differential Regulation of Secreted Phopholipase A2 and
Impact on Oligodendrocyte Death
1,2 2 3 2 4
Amalia Trousson , Joelle Makoukji , Patrice X. Petit , Sophie Bernard , Christian Slomianny , Michael
Schumacher1, Charbel Massaad 1,2*
ˆ
1 UMR788, Inserm and University Paris-Sud 11, IFR 93, Le Kremlin-Bicetre, France, 2 UPR 2228, CNRS and University Paris Descartes, IFR95, Paris, France, 3 Cancer,
Apoptosis, and Mitochondria Team, UMR8104 CNRS, Institut Cochin, Paris, France, 4 Inserm U800 and University Lille 1, Villeneuve d’Ascq, France
Abstract
Background: Oxysterols are oxidized forms of cholesterol. They have been shown to be implicated in cholesterol turnover,
inflammation and in neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis. Glial cells are targets of
oxysterols: they inhibit astrocyte proliferation after brain injury, and we have previously shown that 25-hydroxycholesterol
(25OH) provokes oligodendrocyte apoptosis and stimulates the expression of sPLA2 type IIA (sPLA2-IIA), which has a
protective effect.
Methodology/Principal Findings: As glucocorticoids are well-known for their anti-inflammatory effects, our aim was to
understand their direct effects on oxysterol-induced responses in oligodendrocytes (sPLA2-IIA stimulation and apoptosis).
We demonstrate that the synthetic glucocorticoid dexamethasone (Dex) abolishes the stimulation of sPLA2-IIA by 25-
hydroxycholesterol (25-OH). This inhibition is mediated by the glucocorticoid receptor (GR), which decreases the expression
of the oxysterol receptor Pregnane X Receptor (
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