Evidence for the role of a cathepsin D-like activity in the release of Gal beta 1-4GlcNAc alpha 2-6sialyltransferase from rat and mouse liver in whole-cell systems.
1. Sialyltransferase is a liver Golgi membrane-bound enzyme that is released from the liver under conditions of experimental inflammation. Previous work showed that the action of a cathepsin D-like proteinase was responsible for release of the enzyme from isolated Golgi membranes. This study shows that the same enzyme is responsible for release of sialyltransferase in whole-cell systems. 2. Gal beta 1-4GlcNAc alpha 2-6sialyltransferase (EC 2.4.99.1) was secreted from slices of rat and mouse liver into the incubation medium with larger amounts of activity being secreted from slices of liver from animals suffering from experimental inflammation. 3. The presence in the incubation medium of the cathepsin D proteinase inhibitor, pepstatin A, at 10(-4) M was sufficient to inhibit the release of sialyltransferase into the medium by about 60% after a 6 hr incubation. 4. The release of albumin and alpha 1 acid glycoprotein from rat liver slices, was not affected by the presence of pepstatin A, indicating that the proteinase inhibitor did not affect the synthesis and secretion of typical secretable proteins by the liver. 5. Intraperitoneal injections of pepstatin A into mice prior to preparation of liver slices also resulted in a significant reduction of the secretion of sialyltransferase into the incubation medium. 6. The results from these studies support the idea that a cathepsin D-like proteinase is responsible for the release of sialyltransferase into the extracellular space in whole cells in the rat and the mouse.
McCaffrey
G
G
Department of Chemistry, University of Manitoba, Winnipeg, Canada.
Jamieson
J C
JC
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D009961:Orosomucoid / Q000378:metabolism; D010436:Pepstatins / Q000494:pharmacology; D051381:Rats; D012799:Sialyltransferases / Q000378:metabolism*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D000418:Albumins; D009961:Orosomucoid; D010436:Pepstatins; C014195:Streptomyces pepsin inhibitor; D012799:Sialyltransferases; D002402:Cathepsin D; C031375:pepstatin; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase