Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Matrix metalloproteinases are an important group of zinc enzymes responsible for degradation of the extracellular matrix components such as collagen and proteoglycans in normal embryogenesis and remodeling and in many disease processes such as arthritis, cancer, periodontitis, and osteoporosis. A matrixin family is defined, comprising at least seven members that range in size from Mr 28,000 to 92,000 and are related in gene sequence to collagenase. All family members are secreted as zymogens that lose peptides of about 10,000 daltons upon activation. Latency is due to a conserved cysteine that binds to zinc at the active center. Latency is overcome by physical (chaotropic agents), chemical (HOCl, mercurials), and enzymatic (trypsin, plasmin) treatments that separate the cysteine residue from the zinc. Expression of the metalloproteinases is switched on by a variety of agents acting through regulatory elements of the gene, particularly the AP-1 binding site. A family of protein inhibitors of Mr 28,500 or less binds strongly and stoichiometrically in noncovalent fashion to inhibit members of the family. The serum protein alpha 2-macroglobulin and relatives are also strongly inhibitory.
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PMID:Matrix metalloproteinases and their inhibitors in connective tissue remodeling. 185 Jul 5

Activities of cysteine and trypsin-like proteinase inhibitors and of cathepsin D were measured in mixed saliva of periodontitis patients with conditions of varying severity. Salivary proteinase inhibitor activities were found related, to a certain measure, to the severity of inflammation. Salivary antitryptic activity was somewhat reduced and cysteine proteinase inhibitor activity elevated in patients with non-severe periodontitis. In cases with medium-severe and severe periodontitis salivary proteinase activity was augmenting, approaching the normal value, whereas cysteine proteinase inhibitor level was significantly decreased. A reduction of salivary inhibitor activity was related to the formation of inhibitor-proteinase complexes, whereas a rise of this activity was explained by release of inhibitors from these complexes resulting from dissociation. This is possibly due to the formation of partially cleaved inhibitor form because of cathepsin effects.
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PMID:[The proteinase inhibitors of mixed saliva in periodontitis]. 185 78

The cysteine proteinases cathepsins B and L have the potential to degrade connective tissue in chronic periodontitis and this may progress episodically at individual tooth sites. The activities of cathepsin B- and L-like proteinases in homogenised gingival tissue from control and periodontitis patients were measured biochemically using the selective peptide substrate Z-Phe-Arg-AFC and the selective cathepsin L inhibitor Z-Phe-Phe-CHN2. Each tooth site was divided, where appropriate, into gingival tissue and granulomata. These were assayed separately and the measurements related to the DNA and protein contents of the tissues. Enzyme activity in healthy control tissue was significantly lower than in diseased tissue. Enzyme activity in gingival tissue and total tissue from periodontitis patients decreased with increasing pocket depth, clinical attachment level, gingival index and bleeding index whilst cathepsin B activity in granulomata increased with increasing pocket depth and clinical attachment level but not with increasing gingival index or gingival bleeding index. Mean enzyme activity in gingival tissue was 1.6-2.8 times greater than in granulomata. Mean patient enzyme activity in diseased patients did not correlate positively with their mean pocket depth, clinical attachment level, gingival index or gingival bleeding index. These results are best explained by the probable cellular origins of the enzymes and the likely influence of their serum and tissue inhibitors during the disease process.
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PMID:Cathepsin B- and L-like activities at local gingival sites of chronic periodontitis patients. 189 42

The nature and levels of hemoglobin (Hb)-hydrolyzing acidic proteinases including cathepsin D and cathepsin E, which were most active at pH 3.5-4.0, were enzymatically and immunochemically compared between human and rat neutrophils. By subcellular fractionation and immunoprecipitation with discriminative antibodies specific for each enzyme, cathepsin D was shown to be present in the granular content fraction of both human and rat neutrophils and to account for about 35% of the total Hb-hydrolyzing activity. Cathepsin E was observed mainly in the cytoplasmic fraction of rat neutrophils from peripheral blood and peritoneal exudates and accounted for about 65% of the total activity, but it was not detected in human blood neutrophils. Immunoelectron microscopy on rat neutrophils revealed that cathepsin D was exclusively confined to lysosomes, whereas cathepsin E was localized mainly in the cytoplasmic matrix and often in the perinuclear spaces and the rough endoplasmic reticulum. The non-cathepsin D activity in human neutrophils, which represented about 65% of the total activity, appeared to be due to a serine proteinase, since it was inhibited by diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride and was not inhibited by agents specific for aspartic-, cysteine-, or metallo proteinases. The enzyme(s) responsible for this activity was largely associated with the granular membranes, and a half of it could be described as an integral membrane protein on the basis of phase separation with Triton X-114 at 35 degrees C. The levels of these Hb-hydrolases in gingival crevicular fluid from human chronic inflammatory periodontitis patients were examined in order to clarify their participation in the periodontal tissue breakdown.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of hemoglobin-hydrolyzing acidic proteinases in human and rat neutrophils. 208 32

To clarify roles of lysosomal cysteine proteinases cathepsins B, H and L in pathological destructive process of periodontal tissues, levels of their enzymatic activities were determined in gingival crevicular fluid (GCF) from chronic adult periodontitis patients and from experimental gingivitis subjects. In periodontitis patients, higher levels of cathepsins B, H and L activities were found at sites with more serious signs of the disease activity. The total activity of each enzyme (per unit time) was positively correlated with the GCF volume. However, it had little or no correlation with the probing depth (PD). In contrast, the specific activity of each enzyme in GCF (activity units per mg protein), which reflects the selectivity of enzyme exudation, was negatively correlated with the GCF volume. These results suggest that the cysteine proteinases are selectively released into gingival crevices at a relatively mild stage of periodontitis. In experimental gingivitis subjects, no significant activity of each enzyme was detected in GCF, even when the quantity of GCF was comparable to that from periodontitis patients. These data suggest that no significant amounts of these enzymes are released at experimental gingivitis sites or that a homeostatic mechanism, including regulation by protease inhibitors, may control activities of these enzymes in GCF with acute inflammation.
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PMID:Cathepsins B, H and L activities in gingival crevicular fluid from chronic adult periodontitis patients and experimental gingivitis subjects. 213 19

The cysteine proteinases cathepsins B and L have collagenolytic potential and so have been implicated in connective-tissue breakdown in chronic periodontitis. Synthetic peptide substrates are often used to detect proteolytic enzymes. The action of homogenates of inflamed gingiva tissue against three such substrates of cathepsin B have been characterized here by protease inhibitors. Using the selective reagents ZPheAlaCHN2, BzValLysLysArgAFC, ZAlaArgArgAFC and ZPheArgAFC were susceptible to both cysteine and non-cysteine proteinase activity; the two types of enzymes had acidic and alkaline pH optima, respectively. The action of other inhibitors at acidic pH indicated the involvement of cathepsin B and, to a lesser extent, cathepsin L. The enzyme active at alkaline pH was a serine proteinase; it resembled glandular kallikrein in its inhibitor response and its ability to hydrolyse a fourth substrate, DValLeuArgAFC, but its greater reactivity with BzValLysLysArgAFC and ZAlaArgArgAFC was not consistent with kallikrein. ZPheArgAFC, though less sensitive than BzValLysLysArgAFC to cysteine proteinase action, was far less susceptible to hydrolysis by the serine proteinase and thus appears the best choice for selective assays of cathepsins B and L.
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PMID:Preliminary studies on cysteine and serine proteinase activities in inflamed human gingiva using different 7-amino-4-trifluoromethyl coumarin substrates and protease inhibitors. 348 58

Infection by Porphyromonas gingivalis is strongly associated with adult periodontitis, with proteinases from this bacterium now considered to be important virulence factors. In order to investigate possible pathological functions of these enzymes, we examined the effect of both free and vesicle-bound forms of the two major cysteine proteinases (gingipains) of P. gingivalis on plasma clot formation by using thrombin time (TT) measurements. Both Lys-gingipain (gingipain-K) and Arg-gingipain (gingipain-R) prolonged plasma TT in a dose- and time-dependent manner, and this was also found with vesicles which are the biological carriers of P. gingivalis proteinases. The increase in plasma TT by vesicles could be completely reversed by treatment with nonspecific cysteine proteinase inhibitors but only partially by compounds selective for either gingipain-K or gingipain-R. Preincubation of vesicles with a gingipain-K-specific inhibitor (z-FK-ck) reduced plasma TT more than a gingipain-R-specific inhibitor (leupeptin), suggesting that under physiological conditions gingipain-K was more effective in fibrinogen destruction. Each purified enzyme also markedly increased fibrinogen TT, gingipain-R being fourfold more potent than gingipain-K. However, in plasma, gingipain-R was ineffective because of the inhibitory effect of albumin. These results imply that cysteine proteinases, especially gingipain-K, abrogate the clotting potential of fibrinogen and, therefore, may contribute to the bleeding tendency and to persistent inflammation in periodontitis sites infected with P. gingivalis.
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PMID:Effect of free and vesicle-bound cysteine proteinases of Porphyromonas gingivalis on plasma clot formation: implications for bleeding tendency at periodontitis sites. 759 Nov 49

Infection with Porphyromonas gingivalis is strongly associated with adult periodontitis, and proteinases are considered to be important virulent factors of the bacterium. In order to investigate the function of proteinases in disease development we examined vesicles, a biological carrier of these enzymes, for the generation of vascular permeability enhancement (VPE) activity, believed to correlate with the exudation of gingival crevicular fluid. The vesicles generated VPE activity from human plasma in a dose-dependent manner which could be inhibited 90% by antipain, a specific inhibitor of the Arg-specific cysteine proteinases (Arg-gingipains [RGPs] from P. gingivalis. Incubation of vesicles with high-molecular-weight-kininogen (HMWK)-deficient plasma did not result in VPE activity. On this basis, RGPs associated with vesicles were assumed to be responsible for most of the VPE activity generation via plasma prekallikrein activation and subsequent bradykinin production. The secondary pathway for VPE activity production was dependent on the direct release of bradykinin from HMWK by the concerted action of RGP and a Lys-specific cysteine proteinase (Lys-gingipain [KGP]), also associated with vesicles. These results indicate that RGP and KGP are biologically important VPE factors acting either via prekallikrein activation (RGP) and/or HMWK cleavage (RGP and KGP) to release BK and, thereby, contributing to the production of gingival crevicular fluid at periodontal sites infected with P. gingivalis.
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PMID:Dependence of vascular permeability enhancement on cysteine proteinases in vesicles of Porphyromonas gingivalis. 772 14

Porphyromonas gingivalis contains high concentrations of numerous cysteine proteinases with trypsin-like activity which have been implicated as important virulence factors in adult-onset periodontitis. We have analyzed the subfractions of six P. gingivalis strains for the presence of arginine-X- and lysine-X-specific proteinases (Arg-gingipain [RGP] and Lys-gingipain [KGP]) previously purified from P. gingivalis H66. Western blot (immunoblot) analysis using antibodies produced against RGP and the N-terminal peptides of RGP or the catalytic subunit of KGP indicated that these enzymes are synthesized by the strains studied and exist as multiple molecular mass species. The major forms of RGP were identified as 110-, 95-, 70- to 90-, and 50-kDa proteins, the first two being a complex of the 50-kDa catalytic subunit with hemagglutinins, with or without an added membrane anchorage peptide. The other forms are single-chain enzymes. While the 95- and 50-kDa RGP were found predominantly in culture medium, the 110- and 70- to 90-kDa forms associated with membranous fractions of the bacteria. The predominant form of KGP in all strains was a complex of the 60-kDa catalytic domain with hemagglutinins, and vesicle- and membrane-associated KGP was about 15 kDa larger than the 105-kDa enzyme present in culture media. These data explain the apparent complexity of P. gingivalis proteinases and indicate that in all strains tested there are two identical enzymes, one with arginine-X specificity and the other with lysine-X specificity, which, working in concert, are responsible for the trypsin-like activity associated with this bacterium.
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PMID:The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain. 789 Mar 69

Cystatins are inhibitors of cysteine proteinases and could play a protective and regulatory role under inflammatory conditions. Since total cystatin activity of whole saliva was increased in periodontal patients (Henskens et al., 1993), we wanted to investigate the types or origins of cystatins involved in this increase. Distinct types of cystatins were identified by isoelectric focusing and immunoblotting with specific antibodies against one of the salivary acidic isoforms, cystatin S. and the widely distributed basic cystatin C. Clarified human whole saliva (CHWS) of healthy subjects contained cystatin S, whereas cystatin C was barely detectable. In contrast, in CHWS of gingivitis and periodontitis patients, both cystatin C and S levels were higher. The origin of cystatin activity was investigated by collecting submandibular (SM), sublingual (SL), and parotid (PAR) saliva from seven subjects with mild gingivitis. Total cystatin activity was about five times higher in SM saliva than in PAR saliva. In SM and SL saliva, both cystatins S and C were demonstrated. In contrast, in PAR samples, solely cystatin C was detectable. The introduction of experimental gingivitis in one periodontally healthy subject resulted in the appearance of a cystatin C band in PAR saliva and in an increase of cystatins S and C in SM saliva. We conclude that the previously observed increase of cystatin activity in whole saliva in inflammatory periodontal disease is, at least in part, due to an increased glandular output of both the isoform cystatin S (pI 4.7) and the basic cystatin C (pI 9.0).
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PMID:Cystatins S and C in human whole saliva and in glandular salivas in periodontal health and disease. 792 75


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