Inhibition, by lanthanides, of neutral proteinases secreted by human, rheumatoid synovium.
Fragments of human, rheumatoid synovium were maintained on organ culture for three days under serum-less conditions. Their conditioned media contained collagenolytic, gelatinolytic and caseinolytic activities, which were susceptible to inhibition by lanthanide ions. Of the four lanthanides tested, Sm3+ proved the best inhibitor of gelatinase and caseinase, while La3+ inhibited collagenase the most strongly. Inhibition of collagenase by La3+ was uncompetitive. A direct binding assay confirmed the greater association between collagen fibrils and collagenase in the presence of La3+. Ca2+ was not required for binding of the uninhibited enzyme to collagen, but acted to stabilize collagenase against thermoinactivation.
Evans
C H
CH
Ridella
J D
JD
D001172:Arthritis, Rheumatoid / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology; D018093:Gelatinases; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008666:Metalloendopeptidases; D008674:Metals, Rare Earth / Q000494:pharmacology*; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors; D010434:Pepsin A / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors; D013583:Synovial Membrane / Q000201:enzymology*
D008674:Metals, Rare Earth; D011480:Protease Inhibitors; D007811:Lanthanum; D010434:Pepsin A; D018093:Gelatinases; D008666:Metalloendopeptidases; C030895:caseinase; D003012:Microbial Collagenase; D002118:Calcium