calpastatin and Carbon-Tetrachloride-Poisoning

Rat intoxication with a single dose of the hepatotoxin carbon tetrachloride induces a significant modification of liver protein kinase C total activity which depends on the degree of the intrahepatocyte oxidative unbalance provoked by various concentrations of the haloalkane. Low carbon tetrachloride amounts stimulate total protein kinase C activity, while one order of magnitude higher amounts exert strong enzyme inhibition. The latter effect is due to an early inactivation followed with progress of time by a proteolytic degradation of the enzyme. A pathological recruitment of the calcium-dependent protein kinase C regulatory enzymes calpain and calpastatin appears responsible for protein kinase C loss. The prolonged excess of cytosolic calcium which characterizes the single high dose carbon tetrachloride poisoning also leads to inactivation of calpain II and calpastatin in a time-dependent manner.

Topics: Animals; Calcium-Binding Proteins; Calpain; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Dose-Response Relationship, Drug; Immunoblotting; Isoenzymes; Kinetics; Liver; Male; Oxygen Consumption; Protein Kinase C; Rats; Rats, Wistar; Time Factors