Trophic actions of extracellular ATP: gene expression profiling by DNA array analysis

In addition to Professor Burnstock's work on the short-term signaling actio ns of extracellular nucleotides and nucleosides, Geoff has had a long-stand ing interest in trophic actions of purines in development and in pathophysi ological conditions which has been instrumental in encouraging my work in t his area. The trophic actions of extracellular ATP, alone or in combination with polypeptide growth factors, may play an important role in brain devel opment and may contribute to the reactive gliosis that accompanies brain in jury and neurodegeneration. P2Y receptors in astrocytes are coupled to the ERK/MAPK cascade, a signal transduction mechanism crucial for cellular prol iferation and differentiation. The mitogenic signaling pathway from P2Y rec eptors to ERK involves phospholipase D and a calcium-independent PKC isofor m, PKC delta. DNA array analysis reveals a number of changes in gene expres sion after P2Y receptor occupancy, indicating that this methodology will be a powerful tool in understanding the mechanisms underlying the trophic act ions of extracellular nucleotides and nucleosides, (C) 2000 Published by El sevier Science B.V. All rights reserved.