The selective role of cathepsins B and D in the lysosomal degradation of endogenous and exogenous proteins.
A selective inhibitor of cathepsin B, a derivative of E-64 (compound CA-074), and pepstatin-asialofetuin, a potent inhibitor of cathepsin D, were used for an in vivo study of the selective role of these proteinases in lysosomal proteolysis. Administration of compound CA-074 or pepstatinasialofetuin to rats caused only a slight shift of the lysosomal density and no increase in sequestered enzymes in the autolysosomal fraction, although cathepsin B or D activity in the liver was markedly inhibited. These treatments also had little effect on the inhibition of the degradation of endocytosed FITC-labeled asialofetuin. In contrast, leupeptin treatment caused marked inhibition of lysosomal degradation of endogenous and exogenous proteins. These results suggest a small contribution of cathepsins B and D to the initiation of lysosomal proteolysis.
Kominami
E
E
Department of Biochemistry, School of Medicine, Juntendo University, Tokyo, Japan.
Ueno
T
T
Muno
D
D
Katunuma
N
N
D000818:Animals; D001212:Asialoglycoproteins; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002402:Cathepsin D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D060748:Fetuins; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D010436:Pepstatins / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013861:Thiocyanates; D000509:alpha-Fetoproteins / Q000378:metabolism / Q000494:pharmacology
D001212:Asialoglycoproteins; D004151:Dipeptides; D060748:Fetuins; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007976:Leupeptins; D010436:Pepstatins; D011506:Proteins; D013861:Thiocyanates; D000509:alpha-Fetoproteins; C017029:asialofetuin; C014195:Streptomyces pepsin inhibitor; C068250:N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline; D002401:Cathepsin B; D002402:Cathepsin D; D016650:Fluorescein-5-isothiocyanate; C032854:leupeptin; C031375:pepstatin