Antisense inhibition of glial S100 beta production results in alterations in cell morphology, cytoskeletal organization, and cell proliferation.
The phenotypic effects of selectively decreasing the levels of S100 beta in cultured glial cells were analyzed. Two separate antisense approaches were utilized for inhibition of S100 beta production: analysis of clonal isolates of rat C6 glioma cells containing an S100 beta antisense gene under the control of a dexamethasone-inducible promoter, and analysis of C6 cells treated with S100 beta antisense oligodeoxynucleotides. Both antisense methods resulted in a decrease in S100 beta levels in the cell, as measured by RIA. The inhibition of S100 beta production correlated with three alterations in cellular phenotype: (a) a flattened cell morphology; (b) a more organized microfilament network; and (c) a decrease in cell growth rate. The studies describe here provide direct evidence for an involvement of S100 beta in glial cell structure and function, and suggest potential in vivo roles for S100 beta in regulation of glial cell morphology, cytoskeletal organization, and cell proliferation.
Selinfreund
R H
RH
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232-6600.
Barger
S W
SW
Welsh
M J
MJ
Van Eldik
L J
LJ
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D003599:Cytoskeleton / Q000648:ultrastructure; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005910:Glioma; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism; D016376:Oligonucleotides, Antisense; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D009414:Nerve Growth Factors; D016376:Oligonucleotides, Antisense; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D003907:Dexamethasone