SHP-1 expression in avian mixed neural/glial cultures.
The central nervous system response to injury includes astrocyte proliferation and hypertrophy as well as microglial activation and proliferation. However, not all glial cells enter the cell cycle following damage, and the mechanism that determines which glial cells will proliferate and which will remain quiescent has yet to be elucidated. Protein tyrosine phosphorylation has been shown to play an important role in the regulation of the cell cycle in a number of different systems and has been implicated in both astrocyte proliferation and differentiation. Of particular interest is the protein tyrosine phosphatase SHP-1 (Src homology 2-containing protein tyrosine phosphatase 1), which: (1) modulates cellular proliferation in the hematopoietic system, (2) is involved in various growth factor second messenger signaling cascades, and (3) has been demonstrated by our laboratory to increase in immunoreactivity within a subpopulation of astrocytes following deafferentation of the chicken auditory brainstem. These SHP-1+ cells appear to be those which fail to enter the cell cycle following deafferentation. The present study examines whether manipulation of cellular proliferation in vitro modifies the expression of SHP-1 immunoreactivity in mixed neural/glial cultures of the avian auditory brainstem. In addition, the effect of the protein tyrosine phosphatase inhibitor sodium orthovanadate on cellular proliferation was assessed in these cultures. Our results demonstrate that SHP-1 expression can be modulated by changes in proliferation and that inhibiting tyrosine phosphatase activity results in increased proliferation. Taken together, these results indicate that SHP-1 may play central role in negatively regulating glial proliferation following injury.
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, University of Montana, Missoula, Montana 59812-1552, USA.
Jeffrey D
JD
Sorbel
Diane M
DM
Brooks
Diana I
DI
Lurie
D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002642:Chick Embryo; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D009457:Neuroglia / Q000201:enzymology*; D009474:Neurons / Q000201:enzymology*; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000032:analysis*
D047908:Intracellular Signaling Peptides and Proteins; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases