RESUMEN
BACKGROUND: Oral health is integral to systemic health. There is a growing body of evidence of an association between periodontal and systemic diseases. The aim of the study was to evaluate the awareness of dentists regarding link between oral and systemic health. MATERIALS AND METHODS: Data was collected using a self-administered pilot-tested questionnaire. Dentists awareness about link between oral and systemic link was assessed on five point likert scale. Data was entered and analysed using SPSS. RESULTS: Of the 588 dentists, 500 completed the questionnaire (response rate 85.03%). About 93% of the participants (mean age 25.82 ± 4.21 years) agreed that oral health was associated with systemic health. Most dentists were aware of a connection between periodontal disease and diabetes (84.4%) and heart disease (70.2%). Similarly, 85.6% believed in the negative impact of oral disease on the quality of life of patients. More female than male dentists were aware of the relationship between periodontal disease and adverse pregnancy outcomes, diabetes, and rheumatoid arthritis (P < 0.001). Most dentists (97%) believed that more patients would seek oral care if they were aware of the oral-systemic link. After adjustments, private dentists were 4.65 times more likely than public dentists to believe in improving access to oral care with increased patient awareness of the oral-systemic connection (P = 0.011). CONCLUSIONS: Most dentists were aware of the oral-systemic link. They believed that patients' access to oral care would improve if they were aware of a connection between oral and systemic health. Therefore, patients should be informed of the oral-systemic link to improve their oral health.
RESUMEN
Tropoelastin (TE), the soluble monomer of elastin, is synthesized by elastogenic cells, such as chondrocytes, fibroblasts, and smooth muscle cells (SMCs). The C-terminal domain of TE interacts with cell receptors, and these interactions play critical roles in elastic fiber assembly. We recently found that oxidation of TE prevents elastic fiber assembly. Here, we examined the effects of oxidation of TE on cell interactions. We found that SMCs bind to TE through heparan sulfate (HS), whereas fetal lung fibroblasts (WI-38 cells) bind through integrin α(v)ß(3) and HS. In addition, we found that oxidation of TE by peroxynitrite (ONOO(-)) prevented binding of SMCs and WI-38 cells and other elastogenic cells, human dermal fibroblasts and fetal bovine chondrocytes. Because the C-terminal domain of TE has binding sites for both HS and integrin, we examined the effects of oxidation of a synthetic peptide derived from the C-terminal 25 amino acids of TE (CT-25) on cell binding. The CT-25 peptide contains the only two Cys residues in TE juxtaposed to a cluster of positively charged residues (RKRK) that are important for cell binding. ONOO(-) treatment of the CT-25 peptide prevented cell binding, whereas reduction of the CT-25 peptide had no effect. Mass spectrometric and circular dichroism spectroscopic analyses showed that ONOO(-) treatment modified both Cys residues in the CT-25 peptide to sulfonic acid derivatives, without altering the secondary structure. These data suggest that the mechanism by which ONOO(-) prevents cell binding to TE is by introducing negatively charged sulfonic acid residues near the positively charged cluster.
Asunto(s)
Condrocitos/metabolismo , Fibroblastos/metabolismo , Miocitos del Músculo Liso/metabolismo , Ácido Peroxinitroso/metabolismo , Procesamiento Proteico-Postraduccional/fisiología , Tropoelastina/metabolismo , Animales , Bovinos , Adhesión Celular/fisiología , Línea Celular , Humanos , Integrina alfaVbeta3/metabolismo , Oxidación-Reducción , Péptidos/química , Péptidos/metabolismo , Ácido Peroxinitroso/química , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Tropoelastina/químicaRESUMEN
Elastic fibers are extracellular structures that provide stretch and recoil properties of tissues, such as lungs, arteries, and skin. Elastin is the predominant component of elastic fibers. Tropoelastin (TE), the precursor of elastin, is synthesized mainly during late fetal and early postnatal stages. The turnover of elastin in normal adult tissues is minimal. However, in several pathological conditions often associated with inflammation and oxidative stress, elastogenesis is re-initiated, but newly synthesized elastic fibers appear abnormal. We sought to determine the effects of reactive oxygen and nitrogen species (ROS/RNS) on the assembly of TE into elastic fibers. Immunoblot analyses showed that TE is oxidatively and nitrosatively modified by peroxynitrite (ONOO(-)) and hypochlorous acid (HOCl) and by activated monocytes and macrophages via release of ONOO(-) and HOCl. In an in vitro elastic fiber assembly model, oxidatively modified TE was unable to form elastic fibers. Oxidation of TE enhanced coacervation, an early step in elastic fiber assembly, but reduced cross-linking and interactions with other proteins required for elastic fiber assembly, including fibulin-4, fibulin-5, and fibrillin-2. These findings establish that ROS/RNS can modify TE and that these modifications affect the assembly of elastic fibers. Thus, we speculate that oxidative stress may contribute to the abnormal structure and function of elastic fibers in pathological conditions.
Asunto(s)
Tejido Elástico/metabolismo , Estrés Oxidativo , Ácido Peroxinitroso/metabolismo , Tropoelastina/metabolismo , Animales , Línea Celular , Células Cultivadas , Fibrilina-2 , Fibrilinas , Humanos , Ácido Hipocloroso/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Monocitos/metabolismo , Oxidación-Reducción , Procesamiento Proteico-Postraduccional , Tropoelastina/genéticaRESUMEN
Cancer stem cells (CSCs) are rare tumor cells that have the potential to proliferate, self-renew and induce tumorigenesis. Over the past few years, CSCs have been isolated from several different tumors and when implanted into immune-deficient mice, generate tumors that are identical to the parental tumors. In this review, we summarize the current literature on CSCs, which suggests that since these cells have the ability to drive tumor formation, specifically targeting them may lead to more effective therapies against tumors.
Asunto(s)
Neoplasias/patología , Neoplasias/prevención & control , Células Madre Neoplásicas/patología , Animales , Transformación Celular Neoplásica , Humanos , Neoplasias/metabolismoRESUMEN
In this study, we attempted to understand the mechanism of regulation of the activity and allosteric behavior of the pyruvate kinase M(2) enzyme and two of its missense mutations, H391Y and K422R, found in cells from Bloom syndrome patients, prone to develop cancer. Results show that despite the presence of mutations in the intersubunit contact domain, the K422R and H391Y mutant proteins maintained their homotetrameric structure, similar to the wild-type protein, but showed a loss of activity of 75 and 20%, respectively. Interestingly, H391Y showed a 6-fold increase in affinity for its substrate phosphoenolpyruvate and behaved like a non-allosteric protein with compromised cooperative binding. However, the affinity for phosphoenolpyruvate was lost significantly in K422R. Unlike K422R, H391Y showed enhanced thermal stability, stability over a range of pH values, a lesser effect of the allosteric inhibitor Phe, and resistance toward structural alteration upon binding of the activator (fructose 1,6-bisphosphate) and inhibitor (Phe). Both mutants showed a slight shift in the pH optimum from 7.4 to 7.0. Although this study signifies the importance of conserved amino acid residues in long-range communications between the subunits of multimeric proteins, the altered behavior of mutants is suggestive of their probable role in tumor-promoting growth and metabolism in Bloom syndrome patients with defective pyruvate kinase M(2).
Asunto(s)
Mutación Missense , Piruvato Quinasa/química , Sustitución de Aminoácidos , Síndrome de Bloom/enzimología , Síndrome de Bloom/genética , Estabilidad de Enzimas/genética , Humanos , Concentración de Iones de Hidrógeno , Neoplasias/enzimología , Neoplasias/genética , Estructura Cuaternaria de Proteína/genética , Estructura Terciaria de Proteína/genética , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismoRESUMEN
The orderly recruitment, retention, and disassembly of DNA damage response proteins at sites of damaged DNA is a conserved process throughout eukaryotic evolution. The recruitment and retention of DNA repair factors in foci is mediated by a complex network of protein-protein interactions; however, the mechanisms of focus disassembly remain to be defined. Mediator of DNA damage checkpoint protein 1 (MDC1) is an early and key component of the genome surveillance network activated by DNA double-strand breaks (DSBs). Here, we investigated the disassembly of MDC1 foci. First, we show that ubiquitylation directs the MDC1 protein for proteasome-dependent degradation. Ubiquitylated MDC1 associates with chromatin before and after exposure of cells to ionizing radiation (IR). In addition, increased MDC1 ubiquitylation in the chromatin fraction is observed in response to IR, which is correlated with a reduction in total MDC1 protein levels. We demonstrate that blocking MDC1 degradation by proteasome inhibitors leads to a persistence of MDC1 foci. Consistent with this observation, chromatin immunoprecipitation experiments reveal increased MDC1 protein at site-specific DSBs. Interestingly, we show that the persistence of MDC1 foci is associated with an abrogated recruitment of the downstream factor BRCA1 in a manner that is RNF8 independent. Collectively, the evidence presented here supports a novel mechanism for the disassembly of MDC1 foci via ubiquitin-proteasome dependent degradation, which appears to be a key step for the efficient assembly of BRCA1 foci.
Asunto(s)
Proteínas Nucleares/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Transactivadores/metabolismo , Ubiquitina/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Daño del ADN , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Humanos , Cinética , Proteínas Nucleares/genética , ARN Interferente Pequeño/genética , Transactivadores/genética , Ubiquitina-Proteína Ligasas , Regulación hacia ArribaRESUMEN
Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.