Regulation of prolyl oligopeptidase activity in regenerating rat liver.
We have previously shown that the naturally occurring polyamines, spermidine and spermine, reverse effectively the in vitro inhibition of prolyl oligopeptidase (POPase) by its endogenous inhibitor by forming a kinetically significant 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 peaked 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 animals with a synthetic POPase inhibitor, Z-Gly-Pro-CHN2 (4 mg/kg), resulted in an obvious suppression of the liver regeneration. These 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.
Yamakawa
N
N
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Fukuoka University, Japan.
Shimeno
H
H
Soeda
S
S
Nagamatsu
A
A
D000595:Amino Acid Sequence; D000818:Animals; D003978:Diazomethane / Q000031:analogs & derivatives / Q000494:pharmacology; D008099:Liver / Q000201:enzymology* / Q000648:ultrastructure; D008115:Liver Regeneration; D008297:Male; D008969:Molecular Sequence Data; D011073:Polyamines / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
D011073:Polyamines; D015842:Serine Proteinase Inhibitors; C047930:N-benzyloxycarbonylglycyl-proline diazomethyl ketone; D003978:Diazomethane; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases