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Oxidized phosphatidylcholine formation and action in oligodendrocytes
Author(s) -
Qin Jingdong,
Testai Fernando D,
Dawson Sylvia,
Kilkus John,
Dawson Glyn
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06231.x
Subject(s) - sphingomyelin , microbiology and biotechnology , ceramide , apoptosis , chemistry , hydrogen peroxide , neurodegeneration , reactive oxygen species , phosphorylcholine , protein kinase b , caspase , phosphatidylserine , biochemistry , programmed cell death , biology , phospholipid , membrane , medicine , disease , pathology
Reactive oxygen species play a major role in neurodegeneration. Increasing concentrations of peroxide induce neural cell death through activation of pro‐apoptotic pathways. We now report that hydrogen peroxide generated sn‐2 oxidized phosphatidylcholine (OxPC) in neonatal rat oligodendrocytes and that synthetic OxPC [1‐palmitoyl‐2‐(5′‐oxo)valeryl‐sn‐glycero‐3 phosphorylcholine, POVPC] also induced apoptosis in neonatal rat oligodendrocytes. POVPC activated caspases 3 and 8, and neutral sphingomyelinase (NSMase) but not acid sphingomyelinase. Downstream pro‐apoptotic pathways activated by POVPC treatment included the Jun N‐terminal kinase proapoptotic cascade and the degradation of phospho‐Akt. Activation of NSMase occurred within 1 h, was blocked by inhibitors of caspase 8, increased mainly C18 and C24:1 ceramides, and appeared to be concentrated in detergent‐resistant microdomains (Rafts). We concluded that OxPC initially activated NSMase and converted sphingomyelin into ceramide to mediate a series of downstream pro‐apoptotic events in oligodendrocytes.