Cell proliferation and anti-oxidant effects of oxytocin and oxytocin receptors: Role of extracellular signal-regulating kinase in astrocyte-like cells

Objectives. Oxytocin (OXT) participates in various physiological functions ranging from reproduction to social and non-social behaviors. Recent studies indicate that OXT affects cell growth and metabolism. Here we characterized the growth stimulating and antioxidant actions of OXT and of OXT receptors (OXTR) in a glial cell-line (U-87MG). Methods. We developed an OXTR-knockdown cell-line (U-87MG KD) to establish the receptor specificity of OXT's actions, and the impact of lacking OXTR on growth and survival in glial cells. The role Extracellular-Signal Regulated Kinases (ERK1/2) on glial cell protection against consequences of oxidative stress, and cell proliferation was investigated. Results. In U-87MG cells, OXT stimulated cell proliferation and increased ERK1/2 phosphorylation. The specific ERK1/2 inhibitor, PD098059, produced marked inhibition of cell proliferation, and antagonized the stimulating effect of OXT on ERK1/2 phosphorylation and on cell proliferation. Slower growth rates and lower levels of phosphorylated ERK1/2 were observed in OXTR-knockdown cells and in U-87MG cells treated with an OXTR antagonist (L-371,257). In addition to increasing cell proliferation, OXT significantly blunted the rise in reactive oxygen species induced by H2O2, and antagonized the reductions in cell viability induced by H2O2 and camptothecin. The cell protective and antioxidant actions of OXT in U-87MG cells were not observed in the OXTR-knockdown cells. Conclusion. OXT stimulates the growth of astrocyte-like cells acting on OXTR via ERK1/2 phosphorylation. The protection against apoptosis and the antioxidant capacity of OXT may contribute to the observed increase in cell proliferation. Oxytocin and OXTR appear to be fundamental for cell growth and viability of glial cells.