Inhibition of 6-hydroxydopamine-induced p53 expression and survival of neuroblastoma cells following interaction with astrocytes

The neurotoxin 6-hydroxydopamine has been used to induce selective dopamine rgic cell death in animal models of Parkinson's disease. The response of ne urons to this toxin has been shown to be greatly influenced by astrocytes. Our laboratory reported previously that human neuroblastoma SH-SY5Y cells b ecame more resistant to the toxicity of 6-hydroxydopamine when co-cultured with mouse astrocytes. This enhanced tolerance required direct and specific adhesion between SH-SY5Y cells and astrocytes. We hypothesized that this i nteraction led to biochemical changes in SH-SY5Y cells, thereby protecting these cells from toxicity. To study these changes, we again co-cultured SH- SY5Y cells with astrocytes and treated them with 6-hydroxydopamine. An opti mized condition of trypsin treatment was employed to separate SH-SY5Y cells from astrocytes quickly. Western blot analysis demonstrated that 6-hydroxy dopamine significantly increased p53 protein in monolayer SH-SY5Y cells gro wn in either regular medium or conditioned medium from astrocytes. This cha nge, however, was nor observed in the group co-cultured with astrocytes. Da ta obtained from the ribonuclease protection assay indicated that similar c hanges also occurred at the transcriptional level. The enhanced resistance of the co-cultured SH-SY5Y cells to the toxicity of 6-hydroxydopamine is at tributed to the ability of astrocytes to prevent the increase of p53 induce d by this toxin. This study demonstrate the significance of the interaction between astrocytes and neurons when they are exposed to neurotoxins, (C) 2 001 IBRO. Published by Elsevier Science Ltd. All rights reserved.