15d-PGJ2 induces apoptosis of mouse oligodendrocyte precursor cells.
BACKGROUND
Prostaglandin (PG) production is associated with inflammation, a major feature in multiple sclerosis (MS) that is characterized by the loss of myelinating oligodendrocytes in the CNS. While PGs have been shown to have relevance in MS, it has not been determined whether PGs have a direct effect on cells within the oligodendrocyte lineage.


METHODS
Undifferentiated or differentiated mouse oligodendrocyte precursor (mOP) cells were treated with PGE2, PGF2alpha, PGD2 or 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2). Cell growth and survival following treatment were examined using cytotoxicity assays and apoptosis criteria. The membrane receptors for PGD2 and the nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma, as well as reactive oxygen species (ROS) in the death mechanism were examined.


RESULTS
PGE2 and PGF2alpha had minimal effects on the growth and survival of mOP cells. In contrast, PGD2 and 15d-PGJ2 induced apoptosis of undifferentiated mOP cells at relatively low micromolar concentrations. 15d-PGJ2 was less toxic to differentiated mOP cells. Apoptosis was independent of membrane receptors for PGD2 and the nuclear receptor PPARgamma. The cytotoxicity of 15d-PGJ2 was associated with the production of ROS and was inversely related to intracellular glutathione (GSH) levels. However, the cytotoxicity of 15d-PGJ2 was not decreased by the free radical scavengers ascorbic acid or alpha-tocopherol.


CONCLUSIONS
Taken together, these results demonstrated that 15d-PGJ2 is toxic to early stage OP cells, suggesting that 15d-PGJ2 may represent a deleterious factor in the natural remyelination process in MS.
Xiang
Zhongmin
Z
CNS Signaling Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. zxiang1@partners.org <zxiang1@partners.org>
Lin
Tong
T
Reeves
Steven A
SA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000502:physiology / Q000633:toxicity; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
C477819:15-deoxyprostaglandin J2; D015230:Prostaglandin D2