Regulation of prolyl oligopeptidase activity in regenerating rat liver

• Published in: Biochimica et Biophysica Acta (BBA) - General Subjects Vol. 1199; no. 3; pp. 279 - 284
• Main Authors: Yamakawa, Naomi, Shimeno, Hiroshi, Soeda, Shinji, Nagamatsu, Atsuo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 21.04.1994; Elsevier BV; Elsevier
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Diazomethane; Diazomethane - analogs & derivatives; Diazomethane - pharmacology; Endogenous inhibitor; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Hydrolases; Liver; Liver - enzymology; Liver - ultrastructure; Liver Regeneration; Male; Molecular Sequence Data; Polyamine; Polyamines; Polyamines - pharmacology; Prolyl oligopeptidase; Prolyl Oligopeptidases; Rats; Rats, Wistar; Regeneration (Rat liver); Serine Endopeptidases; Serine Endopeptidases - physiology; Serine Proteinase Inhibitors; Serine Proteinase Inhibitors - pharmacology; POPase; PBS; Polyamine; SDS; DTT; Prolyl oligopeptidase; Regeneration (Rat liver); TPBS; Z-Gly-Pro-CHN 2; Suc-Gly-Pro-MCA; Gly-Pro-MCA; Endogenous inhibitor; Boc-Phe-Ser-Arg-MCA; AMC; Serine endopeptidases; Rat; Enzyme; Liver; Rodentia; Enzyme inhibitor; Cytosol; Regeneration; Vertebrata; Mammalia; Hydrolases; Proteinases
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(94)90007-8

We have previously shown that the naturally occuring polyamines, spermidine and spermine, reverse effectively the in vitro inhibition of prolyl oligopeptidase (POPase) its endogenous inhibitor by forming a kinetically signifcant complex (Soeda et al., J. Neurochem. (1986) 46, 1304–1307). In this study, we examined changes in the activities of POPase and its endogenous inhibitor and in the concentrations of polyamines during the regeneration of rat liver. POPase activity in the liver cytosol peaked 2 days after partial hepatectomy and then decreased near to control activity by 9 days, without its altered synthetic levels. Total polyamine concentrations also peake at 2 days and remained elevated by 9 days, while cytosolic POPase inhibitor activity was minimal (56% of control) at 2 days. Treatment of the animal with a synthetic POPase inhibitor, Z-Gly-Pro-CHN 2 (4 mg/kg), resulted in an obvious suppression of the liver regeneration. The results imply that the activity of POPase involved in nonlysosomal proteolytic pathway is exquisitely regulated by changes not only in its endogenous inhibitor levels but also in intracellular cationic potentials such as polyamines, and that POPase plays a crucial role for the growth and differentiation of liver cell.