Synergistic Activation of DNA Synthesis in Astrocytes by Fibroblast Growth Factors and Extracellular ATP

Abstract: The effects of extracellular ATP and polypeptide growth factors on DNA synthesis in primary cultures of rat astrocytes have been examined. It was found that ATP acts synergistically with either acidic or basic fibroblast growth factor to stimulate DNA synthesis. The specificity of this effect was demonstrated by the inability of ATP to potentiate DNA synthesis induced by platelet‐derived growth factor or epidermal growth factor. ATP appears to act via P2 purinergic receptors, because (a) it was more effective than adenosine and (b) the synergistic effect was observed with the hydrolysis‐resistant P2 agonists, ADPβS and ATPγS. The evidence suggests that extracellular ATP may be an important factor in regulating the extent of gliosis and, as such, may be involved in mechanisms of neural injury and repair.

[1]  S. Whittemore,et al.  Concurrent isolation and characterization of oligodendrocytes, microglia and astrocytes from adult human spinal cord , 1993, International Journal of Developmental Neuroscience.

[2]  S. Whittemore,et al.  Altered Acidic and Basic Fibroblast Growth Factor Expression Following Spinal Cord Injury , 1993, Experimental Neurology.

[3]  G. Burnstock.  Hypoxia, endothelium, and purines , 1993 .

[4]  F. Edwards,et al.  ATP receptor-mediated synaptic currents in the central nervous system , 1992, Nature.

[5]  M. Rathbone,et al.  Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells , 1992, Neuroscience Research.

[6]  S. Frautschy,et al.  Localization of basic fibroblast growth factor and its mRNA after CNS injury , 1991, Brain Research.

[7]  M. Jaye,et al.  Differential Effects of Acidic and Basic Fibroblast Growth Factors on Spinal Cord Cholinergic, GABAergic, and Glutamatergic Neurons , 1991, Journal of neurochemistry.

[8]  F. Eckenstein,et al.  Acidic and basic fibroblast growth factors in the nervous system: distribution and differential alteration of levels after injury of central versus peripheral nerve , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  J. Krebs,et al.  Microglial mitogens are produced in the developing and injured mammalian brain , 1991, The Journal of cell biology.

[10]  L. Heppel,et al.  Extracellular ATP is a mitogen for 3T3, 3T6, and A431 cells and acts synergistically with other growth factors. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  Yves-Alain Barde,et al.  Trophic factors and neuronal survival , 1989, Neuron.

[12]  S. Finklestein,et al.  Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds , 1988, Brain Research.

[13]  G. Labourdette,et al.  Comparison of the morphological effects of acidic and basic fibroblast growth factors on rat astroblasts in culture , 1988, Journal of neuroscience research.

[14]  C. Cotman,et al.  Early release of glia maturation factor and acidic fibroblast growth factor after rat brain injury , 1988, Neuroscience Letters.

[15]  V. Yong,et al.  A new double labelling immunofluorescence technique for the determination of proliferation of human astrocytes in culture , 1987, Journal of Neuroscience Methods.

[16]  E. Rozengurt.  Early signals in the mitogenic response. , 1986, Science.

[17]  J. L. Gordon.  Extracellular ATP: effects, sources and fate. , 1986, The Biochemical journal.

[18]  B. Pettmann,et al.  Purification of two astroglial growth factors from bovine brain , 1985, FEBS letters.

[19]  M. Norenberg,et al.  Morphologic Effects of Ammonia on Primary Astrocyte Cultures. I. Light Microscopic Studies , 1985, Journal of neuropathology and experimental neurology.

[20]  M. Hatten,et al.  Astroglia in CNS injury , 1991, Glia.

[21]  T. Maciag,et al.  The heparin-binding (fibroblast) growth factor family of proteins. , 1989, Annual review of biochemistry.

[22]  P. Reier,et al.  Astrocyte activation and fibrous gliosis: glial fibrillary acidic protein immunostaining of astrocytes following intraspinal cord grafting of fetal CNS tissue. , 1987, Progress in brain research.

[23]  G. Burnstock.  A basis for distinguishing two types of purinergic receptor , 1978 .