Journal article
Platelet-Derived Growth Factor-Mediated Signal Transduction Underlying Astrocyte Proliferation: Site of Ethanol Action
The Journal of neuroscience, Vol.19(22), pp.10014-10025
11/15/1999
DOI: 10.1523/JNEUROSCI.19-22-10014.1999
PMCID: PMC6782990
PMID: 10559409
Abstract
Platelet-derived growth factor (PDGF) is a critical regulator of cell proliferation. Because ethanol inhibits cell proliferation in vivo and in vitro, we hypothesize that ethanol-induced inhibition results from differential interference with signal transduction pathways activated by PDGF. Cultured cortical astrocytes were used to examine the effects of ethanol on PDGF-mediated signal transduction, on the expression of two PDGF monomers (A- and B-chains), and on the expression of two PDGF receptor subunits (PDGFalphar and PDGFbetar). PDGF-B chain homodimer (PDGF-BB), and to a lesser extent PDGF-A chain homodimer (PDGF-AA), stimulated the proliferation of astrocytes raised in a serum-free medium. Ethanol attenuated these actions in a concentration-dependent manner. Ethanol inhibited both PDGF-AA- and PDGF-BB-mediated phosphorylation of PDGFalphar, but it had little effect on PDGFbetar autophosphorylation. Likewise, ethanol abolished the association of PDGFalphar to Ras GTPase-activating protein (Ras-GAP), but it did not affect the binding of Ras-GAP to PDGFbetar. PDGF stimulated the activities of mitogen-activated protein kinase (MAPK) in protein kinase C (PKC) independent and dependent manners. Ethanol inhibited the PKC-independent, acute activation of MAPK; however, it stimulated the PKC-dependent, sustained activation of MAPK. The expression of neither ligand was altered by exposure to ethanol for 3 d. Moreover, such treatment specifically upregulated PDGFalphar expression in a concentration-dependent manner. It did not, however, affect the binding affinity of either receptor. Thus, the signal transduction pathways initiated by PDGF-AA and PDGF-BB were differentially affected by ethanol. This differential vulnerability resulted from the preferential effects of ethanol on PDGFalphar autophosphorylation. Hence, ethanol-induced alterations are transduced through specific receptors of mitogenic growth factors.
Details
- Title: Subtitle
- Platelet-Derived Growth Factor-Mediated Signal Transduction Underlying Astrocyte Proliferation: Site of Ethanol Action
- Creators
- Jia Luo - University of IowaMichael W Miller - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.19(22), pp.10014-10025
- DOI
- 10.1523/JNEUROSCI.19-22-10014.1999
- PMID
- 10559409
- PMCID
- PMC6782990
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Language
- English
- Date published
- 11/15/1999
- Academic Unit
- Pathology
- Record Identifier
- 9984186499602771
Metrics
7 Record Views