Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 40 white rats the spontaneous parodontitis was induced and the long-lasting effect of a complex of coenzyme vitamins was studied in their water solution daily application to oral mucosa for a month. This normalized the blood acid-base balance, CTK functional activity, activated the NADP-dependent ICDH, increased the tissues oxidative potencies, thus preventing the jaw alveolar processus atrophy.
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PMID:[Normalization of metabolic disorders in periodontitis using a complex of coenzyme vitamins]. 274 84

Extraction of a tooth necessitated by factors such as developmental problems, trauma, severe periodontal disease and endodontic problems often causes deformities of the residual alveolar ridge in the maxillary anterior region. These cases are usually difficult to restore prosthetically and they result in poor esthetics and insufficient occlusal function. This study investigated the efficacy of root form bioactive glass cones implanted into (a) artificial sockets produced by bone splitting of previous extraction sites (group BS) and (b) fresh extraction sockets (group FES). We included conventional extraction sockets sutured without implanting the root form bioactive glass cones as a control (group C). A total of 16 patients were treated for whom extractions had been indicated due to severe periodontitis. 6 patients with 7 implant sites having Class II or III alveolar ridge deformities comprised the BS group. 5 patients with 10 implant sites comprised the FES group. Group C, comprised 5 patients with 10 extraction sites. Alveolar ridge width and height measurements were obtained using study casts preoperatively, immediately postoperatively, and at 3 and 12 months after operation. In the BS group, while the width of the alveolar ridge increased by 2.8+/-1.18 mm immediately after ridge augmentation procedure and by 2.4+/-0.93 mm at 1 year after operation (p<0.01), the height of the alveolar ridge increased by 1.8+/-1.99 mm and 1.4+/-1.74 mm respectively (p<0.05). In the FES group, the differences between preoperative original ridge height and width and postoperative measurements were not statistically significant, which demonstrated the efficiency of this method in preserving the alveolar ridge. In group C, while alveolar ridge width after 12 months had not significantly changed, alveolar ridge height decreased significantly (1.35+/-1.05 mm, p<0.01). After 12 months, no dehiscences were detected and the differences in height between the groups remained significant. The results of this study indicate that this procedure is efficient in reconstructing alveolar ridges deformed as a result of extraction, particularly relevant in relation to preparation for subsequent restorative treatment.
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PMID:Alveolar ridge reconstruction and/or preservation using root form bioglass cones. 979 57

Adhesive interactions of cells are critical to tissue integrity. We show that infection with Porphyromonas gingivalis, a major pathogen in the periodontal disease periodontitis, interferes with both cell-matrix and cell-cell adhesion in the oral keratinocyte cell line HOK-16. Thus, infected cells showed reduced adhesion to extracellular matrix, changes in morphology from spread to rounded, and impaired motility on purified matrices in Transwell migration assays and scratch assays. Western blot analysis of P. gingivalis-challenged HOK-16 cells revealed proteolysis of focal contact components (e.g., focal adhesion kinase), adherens junction proteins (e.g., catenins), and adhesion signaling molecules (e.g., the tyrosine kinase SRC). Proteolysis was selective, since important components of adherens junctions (E-cadherin) or signaling molecules (extracellular signal-regulated kinases ERK1/2) were not degraded. The virulence factors gingipains, cysteine proteinases expressed by P. gingivalis, are likely responsible for this proteolytic attack, since they directly digested specific proteins in pull-down experiments, and their proteolytic activity was blocked by the cysteine proteinase inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone and also by a caspase inhibitor. Proteolysis was strain dependent, such that ATCC 33277 and 381 had high proteolytic potential, whereas W50 showed almost no proteolytic activity. These findings may help explain the formation of gingival pockets between cementum and periodontal epithelium, a hallmark of periodontitis. Furthermore, they illustrate a new pathogenetic paradigm of infection whereby bacteria may disrupt the integrity of epithelia.
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PMID:Discrete proteolysis of focal contact and adherens junction components in Porphyromonas gingivalis-infected oral keratinocytes: a strategy for cell adhesion and migration disabling. 1222 16

Epidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogen Porphyromonas gingivalis on pregnancy outcomes. Female BALB/c mice were inoculated with heat-killed P. gingivalis (10(9) CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis (10(7) CFU) (n = 20) or broth (control; n = 8) and sacrificed at GD 16.5. Fetal growth restriction (FGR, <0.46 g) was defined as fetuses with weights 2 standard deviations (SD) smaller than controls (0.56 +/- 0.05 g [mean +/- SD]). Among the 20 challenged mice, 8 had both normal-weight (0.51 +/- 0.11 g) and FGR (0.34 +/- 0.1 g) fetuses within the same litter. All other challenged dams had normal-weight fetuses (0.57 +/- 0.04 g). Maternal liver, uterus, and spleen samples were examined for P. gingivalis DNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals for P. gingivalis in liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative for P. gingivalis DNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interleukin-10 levels were significantly reduced compared to levels in dams with normal fetuses. P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate that P. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.
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PMID:Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice. 1293 59

Porphyromonas gingivalis is a predominant periodontal pathogen that expresses a number of potential virulence factors involved in the pathogenesis of periodontitis. Gingival epithelial cells are spontaneously exposed to bacterial attacks and function to prevent invasion by bacteria into deeper tissues. P. gingivalis fimbriae are a critical factor for mediation of interaction of the organism with host tissues, as they promote both bacterial adhesion to and invasion of targeted sites. Fimbriae are capable of binding to human salivary components, extracellular matrix proteins, and commensal bacteria, while they also strongly adhere to cellular alpha5beta1-integrin. Following adhesion to alpha5beta1-integrin, P. gingivalis is captured by cellular pseudopodia, which enables invagination through an actin-mediated pathway. The invasive event has been reported to require host cellular dynamin, actin fibers, microtubules, and lipid rafts. Following passage through the epithelial barrier, the intracellular pathogen impairs cellular function. Fimbriae are classified into 6 genotypes (types I to V and Ib) based on the diversity of the fimA genes encoding each fimbria subunit, and intracellular P. gingivalis with type II fimbriae has been found to clearly degrade integrin-related signaling molecules, paxillin, and focal adhesion kinase, which disables cellular migration and proliferation. These events are considered to integrate the bacterial strategy for persistence in periodontal tissues.
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PMID:Disruption of epithelial barrier and impairment of cellular function by Porphyromonas gingivalis. 1748 50

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis.
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PMID:Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment. 1973 99

Mucocutaneous findings in 150 HIV+ve cases (F, 79; M, 71) were evaluated over a one-year period. Mucocutaneous manifestations were seen in 96% with 2.9 mean number of dermatoses and mean cluster of differentiation (CD4) count of 196.33 cells/mm(3). The highest number of mean dermatoses, 3.29, was seen in individuals with severe immunosuppression. The most common mucocutaneous manifestation seen was candidiasis (35.33%), followed by seborrhoeic dermatitis (31.33%), oral pigmentation (29.33%), xerosis/ichthyosis (22.67%), pyodermas (22%), periodontitis (17.33%) and nail pigmentation (16.67%). Patient stratification according to the WHO immunological staging, according to CD4 counts, showed a statistically significant association (P < 0.05) for candidiasis, scabies, paronychia, oral pigmentation and diffuse hair loss. Nail and oral pigmentary changes, trichomegaly and subcutaneous fungal infections caused by dermatophytes were highlights of the study. Incidences of xerosis/ichthyosis, pyodermas, scabies and molluscum contagiosum reported in our study were higher and pruritic popular eruptions was lower than those in previous Indian studies. Cutaneous neoplasms were not seen in the present study.
Int J STD AIDS 2009 Nov
PMID:Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts. 1977 55

We reported previously that Treponema denticola, one of the periodontal pathogens, suppresses the expression of human beta-defensins (HBDs) in human gingival epithelial cells. To identify the mechanisms involved in this suppression, immortalized and normal human gingival epithelial cells were infected with live or heat-killed T. denticola for 24 h, and then the expression of HBDs was examined by real-time RT-PCR. Live T. denticola suppressed the expression of HBD-3 substantially and also suppressed the expression of HBD-1 and HBD-2. However, heat-killed bacteria did not produce a suppressive effect but instead slightly upregulated the levels of HBD-2 and HBD-3. In contrast to live T. denticola, which reduced the activation of mitogen-activated protein kinase (MAPK) and NF-kappaB within an hour of infection, heat-killed bacteria did not show any inhibitory effect on the MAPK and NF-kappaB signaling pathways. Knockdown of Toll-like receptor 2 (TLR2) via RNA interference abolished the suppressive effect of T. denticola on the expression of HBD-3. Heat-killed T. denticola but not live bacteria could activate TLR2 in CHO/CD14/TLR2 reporter cells, suggesting that T. denticola contains a heat-labile inhibitor(s) of TLR2 in addition to ligands recognized by TLR2. Indeed, live T. denticola was able to inhibit TLR2 activation by Pam(3)CSK. In conclusion, T. denticola suppressed the expression of HBD-3 by inhibiting the TLR2 axis in gingival epithelial cells. These results may provide new insight into the pathogenesis of periodontitis caused by T. denticola.
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PMID:Treponema denticola suppresses expression of human {beta}-defensin-3 in gingival epithelial cells through inhibition of the toll-like receptor 2 axis. 1999 93

Osteoprotegerin (OPG) is a soluble tumor necrosis factor receptor family member that is expressed by a range of cell types in bone as well as in the vasculature. However, the specific role of OPG in the vascular system is unclear. We recently reported that OPG treatment protects endothelial cells from detachment and apoptotic cell death induced by cysteine proteases of Porphyromonas gingivalis, an important pathogen of adult periodontitis. We also found that OPG activates the extracellular signal-regulated kinase (ERK) 1/2, which has been linked to cell survival and angiogenesis. In this study, we demonstrate that exposure to OPG induces a substantial morphological change in human dermal microvascular endothelial cells. Our results show that OPG induced a dose-dependent increase in the length of microtubules, which coincided with the transition of the cells from a polygonal to an elongated shape. Furthermore, we demonstrated that OPG activates signaling pathways that lead to the activation of Src, focal adhesion kinase, and ERK1/2. These findings suggest that OPG regulates at least two distinct pathways: one that induces cell proliferation via ERK signaling and another that induces angiogenesis via Src signaling. The findings of this study suggest that OPG may function as a regulator of angiogenesis.
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PMID:Osteoprotegerin induces cytoskeletal reorganization and activates FAK, Src, and ERK signaling in endothelial cells. 2033 38

We have previously shown that a single nucleotide polymorphism rs11536889 in the 3'-untranslated region (UTR) of TLR4 was associated with periodontitis. In this study the effects of this single nucleotide polymorphism on Toll-like receptor (TLR) 4 expression were investigated. Monocytes from subjects with the C/C genotype expressed higher levels of TLR4 on their surfaces than those from subjects with the other genotypes. Peripheral blood mononuclear cells (PBMCs) from the C/C and G/C subjects secreted higher levels of IL-8 in response to lipopolysaccharide (LPS), a TLR4 ligand, than the cells from the G/G subjects. However, there was no significant difference in TLR4 mRNA levels in PBMCs from the subjects with each genotype. After stimulation with tripalmitoylated CSK(4) (Pam(3)CSK(4)), TLR4 mRNA levels increased in PBMCs from both the C/C and G/G subjects, whereas TLR4 protein levels increased in PBMCs from the C/C but not G/G subjects. Transient transfection of a series of chimeric luciferase constructs revealed that a fragment of 3'-UTR containing rs11536889 G allele, but not C allele, suppressed luciferase activity induced by LPS or IL-6. Two microRNAs, hsa-miR-1236 and hsa-miR-642a, were predicted to bind to rs11536889 G allele. Inhibition of these microRNAs reversed the suppressed luciferase activity. These microRNA inhibitors also up-regulated endogenous TLR4 protein on THP-1 cells (the G/G genotype) after LPS stimulation. Furthermore, mutant microRNAs that bind to the C allele inhibited the luciferase activity of the construct containing the C allele. These results indicate that genetic variation of rs11536889 contributes to translational regulation of TLR4, possibly by binding to microRNAs.
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PMID:A single nucleotide polymorphism in 3'-untranslated region contributes to the regulation of Toll-like receptor 4 translation. 2266 8


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