The anticonvulsant sodium valproate specifically induces the expression of a rat glial heat shock protein which is identified as the collagen type IV receptor.
A potential mechanism for valproate (VPA)-induced increases in glial cell-substratum adhesivity has been demonstrated. Metabolically labelled glioma (C6) and primary astrocytes showed a statistically significant accumulation of protein when cultured in the presence of therapeutic concentrations of VPA (1 mM). This was mainly accounted for by a 10-fold increase in the production of a single polypeptide of 43 kDa molecular weight. Fractionation studies and metabolic labelling with N-acetyl-D-mannosamine showed this to be a sialoglycoprotein which was plasma membrane-bound. VPA-induction of the polypeptide was apparently specific to glioma and primary astrocytes and was not observed in neuroblastoma (neuro-2a), fibroblasts (3T3), pituicytes (GH3) and epithelial cells (NCTC). The 43 kDa component of glia was demonstrated to be the receptor for type IV collagen by binding metabolically labelled and solubilised cells to Sepharose beads which had been individually coated with laminin, fibronectin and type IV collagen. The protein has also been shown to be a heat shock product as metabolically labelled glioma showed a 10-fold increase in its expression when cultured at 42 degrees C. This heat shock induced expression was transient and was in marked contrast to that seen with VPA where it increased with time and was sustained. The expression of 43 kDa is suggested to arise by VPA and heat shock induced delays in cell cycle progression and this is discussed in relation to teratogenic action.
Martin
M L
ML
Department of Pharmacology, University College, Dublin, Eire.
Regan
C M
CM
D000927:Anticonvulsants / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D005910:Glioma; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008970:Molecular Weight; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D038981:Receptors, Collagen; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D006360:Heat-Shock Proteins; D011956:Receptors, Cell Surface; D038981:Receptors, Collagen; D014635:Valproic Acid