Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dental plaque is the major aetiological factor in periodontal diseases and contains several proteolytic enzymes. The origin of these proteinases is, however, poorly studied. This study was undertaken to characterize collagenase present in dental plaque of adult periodontitis patients. Vertebrate-type rather than bacterial-derived collagenase activity was detected in extracts of both supra- and subgingival dental plaque extracts of adult periodontitis patients. Dental plaque collagenase was found to exist predominantly in autoactive form. Dental plaque collagenase from periodontally healthy individuals existed in latent from. Latent dental plaque collagenase from periodontitis lesions could be activated by a 95 kD chymotrypsin-like proteinase from Treponema denticola and human leukocyte cathepsin G but not by human plasmin. Incubation of purified latent leukocyte collagenase with whole cells of Fusobacterium nucleatum, Eubacterium saburreum, Prevotella buccae and Porphyromonas gingivalis, however, did not result to the activation of the enzyme. Doxycycline in vitro inhibited dental plaque collagenase with an IC50-value of 20 microM. Dental plaque collagenase degraded more efficiently type I and II collagens than type III collagen. Western-blot analysis with specific anti-human neutrophil collagenase-antibody revealed that both in supra- and subgingival dental plaque extracts dental plaque collagenase had undergone proteolytic conversion from an 80 kD proform to a 58 kD active form which is associated with catalytic autoactivity as measured by functional collagenase assay. This reflects proteolytic activation of leukocyte collagenase in dental plaque probably by other proteases derived from potent periodontopathogenic bacteria such as T. denticola or other PMN proteases such as cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular source, activation and inhibition of dental plaque collagenase. 759 2

Diabetes produces extensive alterations of collagen metabolism including enhanced gingival collagenase activity. However, the mechanism for this enhanced enzyme activity is unclear. Collagenase is secreted from cells in a latent form and plasmin has been proposed as an important in vivo activator of procollagenase. Plasmin is converted from its precursor, plasminogen, by the proteolytic action of a serine proteinase, plasminogen activator (PA). The current study was therefore undertaken to determine the effect of diabetes on gingival PA activity in the rat. Since doxycycline is a potent collagenase inhibitor, the effect of doxycycline on gingival PA activity was also investigated. Eighteen male, Sprague-Dawley rats were made diabetic by streptozotocin injection (7 mg/100 g). Control rats (N = 8) were sham-treated. Doxycycline (5 mg/day/rat) was administered to 9 of the 18 diabetic rats by gavage on a daily basis. The other 9 diabetic rats were administered with saline. After 3 weeks, blood and gingival tissue were collected from each rat for the determination of glucose level and gingival PA activity. The tissues were then minced and extracted with 5 mM sodium phosphate containing 1% Triton X-100. PA assay was performed using chromatogenic substrate to determine PA activity in the extracts. Gingival PA activity in the diabetic rats was significantly reduced compared to the control (13.5 +/- 1.6 vs. 36.0 +/- 3.3 microunits/100 micrograms protein, P < 0.01). Doxycycline administration to diabetic rats had no effect on the already reduced gingival PA activity (10.4 +/- 3.5 in doxycycline-treated rats vs. 13.5 +/- 1.6 mu units/100 micrograms protein in untreated diabetic rats). PA activities in gingival tissues from the diabetic, nondiabetic control and doxycycline-treated diabetic groups were also demonstrated on zymographs as lytic bands. Regarding the well-known fact that gingival collagenase activity is enhanced during diabetes, our results did not support the notion that this biochemical alteration is attributed to increased activation of procollagenase by PA.
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PMID:Plasminogen activator activity is decreased in rat gingiva during diabetes. 886 12

Tetracyclines inhibit matrix metalloproteinases (MMPs) and reduce infarction volume following cerebral ischemia. In this thesis an involvement of urokinase could be proven. Cerebral ischemia in rats was induced for 3 h followed by 24 h reperfusion (suture model). Each 6 animals received orally either doxycycline or water. Doxycycline treatment began 10 days before ischemia. MMP-2 and MMP-9 were substantially decreased. The possibility of involvement of the endogenous MMP inhibitors in the MMP inhibiting mechanisms was excluded. The plasminogen activator uPA was significantly decreased by doxycycline indicating an MMP inhibiting mechanism including the plasminogen/plasmin system. In the doxycycline group, this resulted in a decreased damage to the cerebral microvessels and less loss of the basal lamina antigen collagen type IV. Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system.
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PMID:Doxycycline inhibits MMPs via modulation of plasminogen activators in focal cerebral ischemia. 1716 29