Diminished activity of protein kinase C in tetanus toxin-treated macrophages and in the spinal cord of mice manifesting generalized tetanus intoxication.

Abstract

In previous studies, we have demonstrated that tetanus toxin (TT) inhibits macrophage (MO) lysozyme secretion and that the inhibition of secretion was not directly linked to perturbation of cytosolic calcium homeostasis. Because MO secretion in response to phorbol myristate acetate, a stimulus that activates protein kinase C (PKC), was inhibited by TT, we examined whether TT might interfere with PKC activity. We report that MOs treated with TT have diminished PKC activity. Purified TT as well as commercial TT diminished PKC activity, whereas heated TT and supernatant from which TT had been removed had no effect on PKC activity. We further examined PKC activity in homogenates of brain and spinal cord from mice manifesting generalized tetanus. Spinal cord cytosolic PKC activity (pmol/mg of protein per min) was depressed in TT-intoxicated mice (87.3 +/- 25) compared with controls (182.6 +/- 47; P less than .02, n = 7). In contrast, cytosolic protein kinase A activity was similar in control- and TT-treated MOs and mice. These results provide the first evidence that PKC activity is diminished during TT intoxication.