25‐hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR

• DOI: 10.1111/j.1471-4159.2009.06009.x
• Publication Date: 2009-02-25T03:36:53Z
• Authors: Amalia Trousson; Sophie Bernard; Patrice X. Petit; Philippe Liere; Antoine Pianos; Khadija El Hadri; Jean‐Marc A. Loba...; M. Said Ghandour; Michel Raymondjean; Michael Schumacher; Charbel Massaad
• Keywords: Oxysterol; Liver X receptor; Pregnane X receptor

In several neurodegenerative diseases of the CNS, oligodendrocytes are implicated in an inflammatory process associated with altered levels oxysterols and enzymes such as secreted phospholipase A2 (sPLA2). view scarce literature related to this topic, we investigated oxysterol effects on these myelinating glial cells. Natural 25-hydroxycholesterol (25-OH; 1 10 microM) oligodendrocyte cell line (158N) morphology triggered apoptosis (75% after 72 h). These were mimicked by 22(S)-OH (1 which does not activate liver X receptor (LXR) but a synthetic LXR ligand (T0901317). Therefore, oxysterol-induced appears be independent LXR. Interestingly, sPLA2 type IIA (sPLA2-IIA) over-expression partially rescued 158N cells from apoptosis. fact, 25-OH, 24(S)-OH, T0901317 stimulated sPLA2-IIA promoter activity line. Accordingly, administration mice enhanced brain extracts twofold. Short interfering RNA strategy allowed establish that stimulation is mediated pregnane (PXR) at high concentration (10 beta basal concentration. Finally, GC coupled mass spectrometry established contain express their biosynthetic enzymes, suggesting they may act through autocrine/paracrine mechanism. Our results show diversity signalling CNS highlight positive LXR/PXR pathway open new perspectives treatment demyelinating diseases.