Secretion and processing mechanisms of procathepsin L in bone resorption.
Secretion of procathepsin L into the culture medium from a bone cell mixture was markedly enhanced by addition of parathyroid hormone (PTH), 1 alpha,25-(OH)2D3 or tumor necrosis factor alpha (TNF alpha). These stimulators of secretion of procathepsin L enhanced bone pit formation, which was inhibited by E-64, but not by CA-074, a specific inhibitor of cathepsin B. Procathepsin L may thus participate in the process of bone collagenolysis during bone resorption. Procathepsin L partially purified from rat long bones under cold conditions was rapidly converted to the mature form under acidic conditions at room temperature. This conversion was inhibited by E-64, suggesting that the procathepsin L secreted into lacunae is catalytically converted to the mature enzyme by cysteine proteinase(s).
Kakegawa
H
H
Institute for Health Sciences, Tokushima Bunri University, Japan.
Tagami
K
K
Ohba
Y
Y
Sumitani
K
K
Kawata
T
T
Katunuma
N
N
D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects / Q000201:enzymology*; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases; D004792:Enzyme Precursors / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D019379:Teriparatide; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D004792:Enzyme Precursors; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D019379:Teriparatide; C068250:N-(3-propylcarbamoyloxirane-2-carbonyl)-isoleucyl-proline; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C063905:procathepsin L; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat; D002117:Calcitriol; D007930:Leucine; C024974:E 64; D002118:Calcium