The alpha linolenic acid oxidative product protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors

Phytoprostanes (PhytoPs) are formed in higher plants from alpha linolenic acid via a nonenzymatic free radical catalyzed pathway similar to that leading to isoprostane formation from arachidonic acid in animal cells. In plants PhytoPs act as endogenous mediators capable of protecting cells from damage under various conditions related to oxidative stress. Since humans are potentially exposed to PhytoPs, which can be ingested through vegetable food or inhaled with pollen, we sought to investigate their potential activities on immature cells of the central nervous system, which are particularly susceptible to oxidative stress. The neuroblastoma SHSY5Y cell line was used as a model for undifferentiated neurons. B1PhytoPs, but not F1PhytoPs, increased the metabolic activity of SHSY5Y cells and protected them from oxidant damage caused by H2O2. Moreover, B1PhytoP induced a moderate depolarisation of mitochondrial inner membrane potential. Both protection and mitochondrial depolarisation were prevented by the PPARg antagonist GW9662. When SHSY5Y cells were induced to differentiate towards a more mature phenotype, they became resistant to B1PhytoP activities. The protective effects of B1PhytoP against oxidant injury appeared to be restricted to immature neuronal cells, since it did not protect oligodendrocyte progenitors from H2O2induced cell damage. However, B1PhytoP increased the metabolic activity of oligodendrocyte progenitors and strongly accelerated their differentiation to immature oligodendrocytes. Again, B1PhytoP induced oligodendrocyte differentiation was at least partially dependent on PPARg activity. Taken together, these data suggest that B1 PhytoP, through mechanisms involving PPARg, can differently affect neuroblasts and oligodendrocyte progenitors thereby conferring neuroprotection against oxidant injury and promoting myelination. (Authors abstract)