Modulation of rat liver protein kinase C during "in vivo" CC14-induced oxidative stress.
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.
Pronzato
M A
MA
Institute of General Pathology, Faculty of Medicine, University of Genova, Italy.
Domenicotti
C
C
Rosso
E
E
Bellocchio
A
A
Patrone
M
M
Marinari
U M
UM
Melloni
E
E
Poli
G
G
D000818:Animals; D002135:Calcium-Binding Proteins / Q000302:isolation & purification; D002154:Calpain / Q000037:antagonists & inhibitors; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D002135:Calcium-Binding Proteins; D007527:Isoenzymes; C033668:calpastatin; D002251:Carbon Tetrachloride; D011493:Protein Kinase C; D002154:Calpain