Changes in carboxylesterase isoenzymes of rat liver microsomes during hepatocarcinogenesis.
Among the three major carboxylesterase isoenzymes, RH1, RL1 and RL2, present in microsomes from normal rat liver, RL2 shows hydrolyzing activity towards 12-O-tetradecanoylphorbol-13-acetate and 1-oleoy1-2-acetyl-rac-glycerol, both activators of protein kinase C. Since protein kinase C has been suggested to be involved in carcinogenesis and cell proliferation, alterations in hepatic microsomal carboxylesterase isoenzymes including RL2 were studied during hepatocarcinogenesis induced by the Solt-Farber model. Alteration of RL2 was determined by measuring acetanilide-hydrolyzing activity, by quantifying the protein amount using the single radial immunodiffusion method, and by activity staining following electrophoresis of liver microsomes. The isoenzyme composition of hepatic microsomal carboxylesterase was changed after partial hepatectomy, and marked decreases in RL2 activity and protein content were observed at 4 weeks, at the time of preneoplastic foci induction. Partial hepatectomy alone also resulted in decreased RL2 activity. These findings suggest that RL2 may be involved in regulation of protein kinase C activity by metabolizing its activators at an early stage of hepatocarcinogenesis in rats.
Maki
T
T
Second Department of Biochemistry, Hirosaki University School of Medicine.
Hosokawa
M
M
Satoh
T
T
Sato
K
K
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
D004075:Diglycerides; D007527:Isoenzymes; D011493:Protein Kinase C; D002265:Carboxylic Ester Hydrolases; D013755:Tetradecanoylphorbol Acetate