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Increase in protein kinase C activity is associated with human fibroblast growth inhibition
Author(s) -
Rogalsky Vitaly,
Todorov German,
Den Tiberius,
Ohnuma Takao
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80608-j
Subject(s) - protein kinase c , dna synthesis , activator (genetics) , stimulation , fibroblast , cell growth , endocrinology , microbiology and biotechnology , tetradecanoylphorbol acetate , medicine , kinase , biology , chemistry , biochemistry , receptor , dna , in vitro
Protein kinase C(PKC) activity and DNA synthesis were measured in human fetal bone marrow fibroblasts following treatment with tumor necrosis factor alpha (TNFα)(500 U/ml) or conditioned media containing natural cell proliferation inhibitor (CM‐NCPI). Treatment with TNFα led to growth stimulation (120 ± 7% of control in 24 h, 141 ± 6% in 72 h). At the same time particulate PKC activity diminished, reaching 55 ± 8% of control in 24 h and remaining at this level at 72 h. CM‐NCPI treatment of the cells resulted in a decrease in DNA synthesis (by 39 ± 6% in 2 h, by 58 ± 5% in 24 h, and by 78 ± 8% in 72 h). This was accompanied by a significant rise in particulate PKC activity which increased over 3‐fold in 2 h, over 5‐fold in 24 h, and up to 11‐fold in 72 h. This 11‐fold elevation was maintained after 2 week exposure of the fibroblasts to CM‐NCPI. The PKC inhibitor neomycin abolished CM‐NCPI induced growth inhibition, whereas PKC activator 12‐ O ‐tetradecanoylphorbol 13‐acetate intensified it. These results suggest that CM‐NCPI acts as PKC activator and that negative growth regulation by extracellular agents may involve stimulation of PKC activity.