Related Experiment Video
Updated: Jul 13, 2026
Derivation of Glial Restricted Precursors from E13 mice
Published on: June 20, 2012
15d-PGJ2 induces apoptosis of mouse oligodendrocyte precursor cells
Zhongmin Xiang1, Tong Lin, Steven A Reeves
1CNS Signaling Laboratory, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. zxiang1@partners.org <zxiang1@partners.org>
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.
Conclusion:
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.
Insights
Prostaglandin 15d-PGJ2 is toxic to early oligodendrocyte precursor cells, potentially hindering myelin repair in multiple sclerosis (MS). This finding highlights a potential detrimental factor in MS pathology and remyelination.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Prostaglandins (PGs) are linked to inflammation in multiple sclerosis (MS), a condition causing oligodendrocyte loss in the central nervous system (CNS).
- The direct impact of PGs on oligodendrocyte lineage cells in MS remains unclear.
Purpose of the Study:
- To investigate the effects of specific prostaglandins (PGs) on mouse oligodendrocyte precursor (mOP) cell growth and survival.
- To elucidate the mechanisms underlying PG-induced cell death in mOP cells.
Main Methods:
- Treatment of undifferentiated and differentiated mOP cells with PGE2, PGF2alpha, PGD2, and 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2).
- Assessment of cell viability using cytotoxicity assays and apoptosis criteria.
- Examination of PGD2 membrane receptors, PPARgamma, reactive oxygen species (ROS), and glutathione (GSH) levels.
Main Results:
- PGE2 and PGF2alpha showed minimal impact on mOP cell survival.
- PGD2 and 15d-PGJ2 induced apoptosis in undifferentiated mOP cells, with 15d-PGJ2 being less toxic to differentiated cells.
- 15d-PGJ2-induced apoptosis involved ROS production and was inversely related to GSH levels, independent of PGD2 receptors and PPARgamma.
Conclusions:
- 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2) exhibits toxicity towards early-stage oligodendrocyte precursor cells.
- This PG may act as a detrimental factor impeding natural remyelination processes in multiple sclerosis (MS).
