Activation of microglia with lipopolysaccharide leads to the prolonged decrease of conventional protein kinase C activity.
The activation of microglia by lipopolysaccharide (LPS) results in the induction of harmful factors including nitric oxide and tumor necrosis factor alpha (TNFalpha). Such microglial activation was suggested to be mediated by PKC activity based on the results of an inhibitor experiment. To clarify the relationship between microglial activation and PKC activity, conventional PKC (cPKC) activity was measured by enzyme-linked immunosorbent assay (ELISA) in LPS-activated microglia. LPS stimulation caused a time- and dose-dependent decrease (70%) of specific activity of cPKC, ascribed to the decreasing amounts of PKCalpha. However, the remaining PKC activity (30%) was sustained despite longer incubation or higher LPS concentration. Therefore, it is suggested that LPS-stimulated microglia require priming by PKC activation for the induction of harmful factors, while only a part (30%) of original PKC activity is sufficient for durable microglial activation.
Nakajima
Kazuyuki
K
Neurochemistry Division, Institute of Life Science, Soka University, 1-236 Tangi-machi, Hachioji, Tokyo 192-8577, Japan. nakajima@t.soka.ac.jp
Kohsaka
Shinichi
S
Tohyama
Yoko
Y
Kurihara
Tadashi
T
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002273:Carcinogens; D004791:Enzyme Inhibitors; D007211:Indoles; D008070:Lipopolysaccharides; D008301:Maleimides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate