title: Selective inhibition of cysteine proteinases by Z-Phe-AlaCH2F suppresses digestion of collagen by fibroblasts and osteoclasts.
abstract: Effects of the selective inhibitor of cathepsins B and L, Z-Phe-AlaCH2F were studied on the degradation of fibrillar collagen by fibroblasts and osteoclasts in cultured rabbit calvariae at the electron microscopic level. Periosteal fibroblasts from inhibitor-treated explants showed a dose-dependent increase of the volume fraction of vacuoles containing cross-banded collagen fibrils. This was a 7-fold increase over control fibroblasts and the ratio of intracellular and extracellular collagen increased from 2 to 43. The presence of collagen-containing vacuoles was also found in some osteoclasts from inhibitor-treated explants (1 microM or more). The inhibitor appeared to have cytotoxic effects at a concentration of 100 microM. It was concluded that this selective inhibitor exerts its effects intralysosomally in living cells, indicating possibilities for in vivo inhibition of protein degradation.
authors.affiliation: Department of Periodontology, ACTA, University of Amsterdam, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: van Noorden
authors.forename: V
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007659:Ketones / Q000494:pharmacology*; D008854:Microscopy, Electron; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D014617:Vacuoles / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D007659:Ketones; C057383:MDL 201053; D003094:Collagen