Nonenzymatic oxygenated metabolites of alpha-linolenic acid B-1- and L-1-phytoprostanes protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors through PPAR-gamma activation

摘要

Phytoprostanes (PhytoP's) are formed in higher plants from alpha-linolenic acid via a nonenzymatic free radical-catalyzed pathway and act as endogenous mediators capable of protecting cells from damage under various conditions related to oxidative stress. Humans are exposed to PhytoP's, as they are present in relevant quantities in vegetable food and pollen. The uptake of PhytoP's through the olfactory epithelium of the nasal mucosa, upon pollen grain inhalation, is of interest as the intranasal pathway is regarded as a direct route of communication between the environment and the brain. On this basis, we sought to investigate the potential activities of PhytoP's on immature cells of the central nervous system, which are particularly susceptible to oxidative stress. In neuroblastoma SH-SY5Y cells, used as a model for undifferentiated neurons, B-1-PhytoP's, but not F-1-PhytoP's, increased cell metabolic activity and protected them from oxidant damage caused by H2O2. Moreover, B-1-PhytoP's induced a moderate depolarization of the mitochondrial inner membrane potential. These effects were prevented by the PPAR-gamma antagonist GW9662. When SH-SY5Y cells were induced to differentiate toward a more mature phenotype, they became resistant to B-1-PhytoP activities. B-1-PhytoP's also influenced immature cells of an oligodendroglial line, as they increased the metabolic activity of oligodendrocyte progenitors and strongly accelerated their differentiation to immature oligodendrocytes, through mechanisms at least partially dependent on PPAR-gamma activity. However, B-1-PhytoP's did not protect oligodendrocyte progenitors against oxidant injury. Taken together, these data suggest that B-1-PhytoP's, through novel mechanisms involving PPAR-gamma, can specifically affect immature brain cells, such as neuroblasts and oligodendrocyte progenitors, thereby conferring neuroprotection against oxidant injury and promoting myelination. (C) 2014 Elsevier Inc. All rights reserved.