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Contents of Volume 1 (2005)

Author index to Volume 1 (2005)

Purinergic Signalling : Volume 1, Issue 3, September 2005

Purinergic Signalling : Volume 1, Issue 2, June 2005

Purinergic Signalling : Volume 1, Issue 1, December 2004

Cell cycle regulation of astrocytes by extracellular nucleotides and fibroblast growth factor-2

Content Provider	Springer Nature Link
Author	Neary, Joseph T. Kang, Yuan Shi, You Fang
Copyright Year	2005
Abstract	Extracellular ATP enhances the mitogenic activity of fibroblast growth factor-2 (FGF2) in astrocytes, but the molecular mechanism underlying this synergistic interaction is not known. To determine whether the potentiating effect of extracellular ATP involves cell cycle control mechanisms, we have measured the expression of cyclins that are induced in different phases of the cell cycle in primary cultures of rat cortical astrocytes. We found that ATP potentiated the ability of FGF2 to stimulate expression of cyclin D1, a regulator of cell cycle entry, as well as cyclin A, a regulator of DNA replication. Because FGF2 and P2 purinergic receptors are coupled to extracellular signal regulated protein kinase (ERK), a key member of a signaling cascade that regulates proliferation, we also investigated the role of ERK in regulating cyclin expression induced by FGF2 and ATP. We found that the potentiating effect of ATP on cyclin expression was significantly reduced by U0126, an inhibitor of MEK, the upstream activator of ERK. P2 receptor agonist studies revealed that UTP enhanced FGF2-induced cyclin expression and mitogenesis whereas 2-methylthioADP was ineffective. By contrast, 2-3-O-(4-benzoyl)-benzoyl-ATP markedly inhibited FGF2-induced mitogenesis. Consistent with opposing effects of P2Y and P2X receptors on mitogenesis, UTP stimulated a transient activation of ERK whereas BzATP stimulated a more sustained ERK signal. These findings suggest that signaling by P2Y receptors, most likely of the purine/pyrimidine subtype, enhance the ability of FGF2 to stimulate entry into a new cell cycle, as well as DNA replication, by an ERK-dependent mechanism, whereas signaling by P2X receptors, possibly the P2X7 subtype, inhibits FGF2-induced mitogenesis in astrocytes. Interactions between P2Y, P2X and polypeptide growth factor signaling pathways may have important implications for CNS development as well as injury and repair.
Starting Page	329
Ending Page	336
Page Count	8
File Format	PDF
ISSN	15739538
Journal	Purinergic Signalling
Volume Number	1
Issue Number	4
e-ISSN	15739546
Language	English
Publisher	Springer Netherlands
Publisher Date	2005-12-03
Publisher Institution	International Purine Club
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	astrocytes cell cycle CNS injury ERK extracellular ATP gliosis P2 purinergic receptors proliferation Biomedicine general Pharmacology/Toxicology Human Physiology Neurosciences Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Cellular and Molecular Neuroscience

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