Role of protein kinase C in glial cell proliferation

Abstract

Phorbol 12-myristate 13-acetate (PMA) has been shown to stimulate DNA synthesis and cell proliferation in a population of glial cells isolated from newborn rat brain. The non-tumor promoter 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), on the other hand, was without an effect. The cultures treated with PMA displayed an extensive process formation and an increase in cell content. The tumor promoter-induced [3H]thymidine incorporation into acid-precipitable material was completely blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), a potent inhibitor of protein kinase C (PKC), thereby suggesting a role for PKC in the control of DNA synthesis in glial cells. Subcellular fractionation and in vitro assay of PKC activity revealed a translocation of the enzyme from cytosol to particulate fraction in PMA-treated cultures.