Proteolytic enzymes

About: Proteolytic enzymes is a research topic. Over the lifetime, 23096 publications have been published within this topic receiving 835544 citations.

Elastolytic Activity in Pulmonary Lavage Fluid from Patients with Adult Respiratory-Distress Syndrome

Abstract: To test the hypothesis that adult respiratory-distress syndrome (ARDS) is related to increased activity of the proteolytic enzyme elastase released from neutrophils in the lung, we determined the differential white-cell count, the elastolytic activity, the source of elastase, and the concentration and activity of the endogenous protease inhibitor alpha-1-antiprotease (α-1-AP) in bronchoalveolar lavage fluid from 23 patients with ARDS and from 55 patients without this syndrome. Neutrophil predominance (>80 per cent) was observed in 18 of 23 patients with ARDS. High elastolytic activity of neutrophil origin was found in 12 of 23 patients with ARDS (52 per cent), in none of 16 normal nonsmokers (P<0.01), in two of 17 normal smokers, and in three of 22 patients with chronic obstructive pulmonary disease. Although there were no significant differences in α-1-AP concentrations, its activity was reduced in eight of nine patients with ARDS and high elastolytic activity. We conclude that in many patients ...

Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells

Abstract: We have studied cells dispersed with proteolytic enzymes from rheumatoid arthritic synovectomy specimens to determine the cell type(s) responsible for joint destruction. Initially 10-50% of these cells adhered to culture dishes within 24 hr and were of two main types: small, round cells and larger, stellate cells. During 1-4 days of culture, 5-25% had Fc receptors and 25-50% showed brisk phagocytosis. Daily producition, per 10(6) cells of collagenase (EC 3.4.24.3) (after trypsin pretreatment) was up to 70 mug of collagen fibrils lysed per min at 37 degrees (70 units), of prostaglandin (PGE2), up to about 1200 ng, and of lysozyme, up to about 100 mug. Under identical conditions of assay, fibroblasts grown from explants of synovium produced no detectable collagenase or lysozyme, and PGE2 was only 2-4 ng. With the dispersed cell preparations, macrophage markers (Fc receptors and lysozyme) were undetectable after 4 days and PGE2 decreased rapidly after about 7 more days. However, collagenase production continued for 3-25 weeks, and in some cultures, after cell passage. At these later stages, large, slow-growing stellate cells were predominant and could phagocytose carbon particles if incubated for greater than 6-8 hr. Indomethacin (14 muM) inhibited PGE2 but stimulated collagenase production whereas dexamethasone (10 nM) inhibited both. Production of PGE2 and collagenase in large amounts in vitro by these cells suggests that they may be involved in joint destruction in vivo. The precise origin of these synovial cells and the mechanisms responsible for the sustained production of collagenase at a high rate remain unidentified.

Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma.

Abstract: Insulin-like growth factor binding protein-3 (IGFBP-3), the major serum carrier protein for the IGFs, is absent from Western ligand blots of seminal plasma, but is detectable by RIA. IGFBP-3 protease activity has recently been described in pregnancy serum. We investigated the possibility that seminal plasma contains an IGFBP-3 protease, by incubating seminal plasma with 125I-labeled human IGFBP-3. Seminal plasma was found to have potent IGFBP-3 protease activity with a cleavage pattern different from that of pregnancy serum. Prostate-specific antigen (PSA) is a serine protease found in semen. Autoradiographs measuring IGFBP-3 protease activity demonstrated that purified PSA cleaved IGFBP-3, yielding a cleavage pattern identical to that of seminal plasma. IGFBP-2 and -4 in seminal plasma were not degraded by PSA. Cleavage of IGFBP-3 by PSA resulted in a marked reduction in the binding affinity of the fragments to IGF-I, but not IGF-II. We speculate that PSA may serve to modulate IGF function within the rep...

Activation of the cell death program by inhibition of proteasome function

Abstract: Activation of proteolytic enzymes, including cysteine proteases of the ced-3/ICE family, is a characteristic feature of the apoptotic program. In contrast, the role of the proteasome as the major nonlysosomal machinery to degrade or process proteins by ATP/ubiquitin-dependent proteolysis in this process is less clear. In human leukemic HL60 cells, inhibition of proteasome-mediated proteolysis by specific proteasomal inhibitors leads to the rapid induction of apoptosis as judged by morphological changes as well as by nuclear condensation and DNA fragmentation. HL60 apoptosis is due to activation of CPP32, a member of the ced-3/ICE family of cysteine proteases, and appears to occur independently from ICE activity. HL60 apoptosis is accompanied by an increase in the concentration of the cyclin-dependent kinase inhibitor p27Kip1. Labeling of the cells by the TUNEL technique demonstrates that HL60 cells undergoing apoptosis are primarily in the G1 phase of the cell cycle. Proteasomal activity therefore appears to be required in proliferating, but not in quiescent, HL60 cells for cell survival as well as normal progression through the cell cycle.