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)

In order to determine the effect of bacterial proteinases on activation of the protein C system, a negative regulator of blood coagulation, two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, a causative bacterium of adult periodontitis, were examined. Each enzyme activated human protein C in a dose- and incubation time-dependent manner. Interestingly, the form of enzyme being composed of a non-covalent complex containing both catalytic and adhesion domains (RgpA) produced activated protein C 14-fold more efficiently than RgpB which contained the catalytic domain alone. The kcat/Km value of RgpA was 18-fold higher than that of RgpB and comparable to that of the thrombin-thrombomodulin complex, the physiological activator of protein C. RgpA catalyzed protein C activation was augmented 1.4-fold by phospholipids, ubiquitous cell membrane components. Furthermore, RgpA, but not RgpB, could activate protein C in plasma and this resulted in a decrease of the protein C concentration in plasma, which is often observed in patients with sepsis during the development of disseminated intravascular coagulation (DIC). These data indicate that RgpA is a more potent activator of protein C than RgpB and suggest that only the former enzyme can cause protein C activation in vivo. The present study further suggests that bacterial proteinases may possibly contribute to the consumption of plasma protein C which predisposes to DIC and/or promotes a thrombotic tendency towards DIC in sepsis.
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PMID:Activation of protein C by arginine-specific cysteine proteinases (gingipains-R) from Porphyromonas gingivalis. 1006 39

Epidermal keratinocytes thrombomodulin (TM) has been shown to regulate thrombin at sites of cutaneous injury in addition to a role for epidermal differentiation. TM, a major anticoagulant proteoglycan of the endothelial cell membrane, is a thrombin receptor that acts as a co-factor for protein C activation. Thrombin has pro-inflammatory effects for periodontitis. However, little is known about TM in gingival tissue with periodontitis. We used immunohistochemistry to examine expression of TM in gingival epithelium from patients with periodontitis. In vitro, we observed TM expression at varying Ca2+ concentrations by confocal laser scanning microscopy, examined the expression of TM mRNA and tested TM co-factor activity. Furthermore, we measured TM concentration in gingival crevicular fluid (GCF) from 11 severe adult cases of periodontitis using enzyme-linked immunosorbent assay. Immunoreactive TM was present in gingival epithelium and junctional epithelium, and was reduced in inflamed gingival epithelium compared to healthy gingival epithelium. Ultrastructurally, TM, including microvilli, was observed on the cell membrane. TM localization in cells cultured in 0.09 mM Ca2+ differed from that in cells exposed to 1.2 mM Ca2+. Northern analysis demonstrated TM mRNA in gingival keratinocytes more than in human umbilical vein endothelial cells (HUVEC). Gingival keratinocytes also facilitated protein C activation by thrombin, although less strongly than HUVEC. TM in GCF at sites with bleeding on probing in patients was significantly elevated (p < 0.001, Student's t-test). TM in gingival epithelium may regulate thrombin activity at sites of coagulation and inflammation with periodontal disease, although inflammation may impair this regulation of thrombin.
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PMID:Expression and activity of thrombomodulin in human gingival epithelium: in vivo and in vitro studies. 1092 69

Since periodontitis is a chronic and inflammatory disease, a number of hypotheses have proposed that it has an etiological or modulating role in cardiovascular disease (CVD). This study aimed to ascertain the changes in the plasma levels of C-reactive protein (CRP) and protein C (PC), a natural anticoagulant also having an anti-inflammatory effect, in patients who have mild-to-severe periodontitis with or without CVD. The test group consisted of 26 patients with CVD and chronic periodontitis and the control group consisted of 26 patients with chronic periodontitis and no systemic disease. In both groups Community Periodontal Index of Treatment Needs scores were recorded and blood samples were collected. CRP levels were significantly high and PC activity was significantly low in the test group compared to the control group (p < 0.001). There was a negative correlation between tooth loss and PC and between CRP and PC. How PC is affected by the inflammatory events and its association with CRP is an active area of investigation.
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PMID:Levels of C-reactive protein and protein C in periodontitis patients with and without cardiovascular disease. 2060 7