In Vivo Translocation and Down‐Regulation of Protein Kinase C Following Intraventricular Administration of Tetanus Toxin

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Abstract
A single intraventricular injection into adult rats of 100 mouse lethal doses of tetanus toxin (TeTox) produces a marked intracellular redistribution of Ca2+/phosphatidylserine (PtdSer)-dependent protein kinase C (PKC) activity. Changes are particularly pronounced in hypothalamus, hippocampus, and spinal cord structures. Translocation of PKC from the inactive cytosolic compartment to a membrane-bound active form is followed by a time-dependent reduction in both total activity and enzyme protein. The down-regulation of PKC activity in the hypothalamus is accompanied by a marked increase in a Ca2+/PtdSer-independent kinase activity, predominantly in the cytosolic fraction. Our data identify PKC as a possible indirect target for TeTox and suggest that down-regulation of the enzyme may provide a clue for tetanus neurotoxicity.