Authors
Advisor(s)
Abstract(s)
Com o desenvolvimento da investigação biomédica e de novas metodologias da Proteómica, foi possível identificar a totalidade de proteínas presentes em células individuais, tecidos e órgãos e relacionar com algumas patologias as alterações destas proteínas nomeadamente a sua presença, ausência, modificações pós-tradução ou quantidade expressa. Para analisar o elevado número de proteínas identificadas em proteomas é necessário recorrer à utilização de ferramentas bioinformáticas para que seja possível integrar a informação obtida e comparar com a informação disponível em diferentes bases de dados. As abordagens referidas são hoje um contributo decisivo para o esclarecimento de mecanismos moleculares e fisiopatológicos.
A Diabetes mellitus tipo 2 (DMT2), por ser uma patologia de etiologia multifactorial prevalente e com implicações relevantes na cavidade oral, principalmente pela dificuldade acrescida de cicatrização, constitui-se como um bom modelo de estudo para a aplicação da Bioinformática Médica à Medicina Dentária.
O presente trabalho é dedicado à análise dos proteoma salivar resultante da DMT2 no sentido de verificar a presença, na saliva, de proteínas alteradas envolvidas na coagulação sanguínea e fibrinólise, dois acontecimentos celulares determinantes para o processo de cicatrização o qual se encontra comprometido no paciente diabético. Esta análise do proteoma salivar é particularmente relevante pois, actualmente, não existem estudos publicados referentes à participação de proteínas da saliva que justifiquem a hipercoagulação e hipofibrinólise que ocorre na DMT2.
O estudo do proteoma salivar da DMT2 permitiu a identificação de dois inibidores importantes de proteases serínicas, alfa-1-antitripsina (SERPINA1) e alfa-2-macroglobulina (A2M), que se encontram alterados na saliva do paciente diabético. Como estes inibidores desempenham um papel regulador decisivo na coagulação/fibrinólise e estando ambos presentes mas em quantidades alteradas, poderão constituir uma das principais causas para a dificuldade de cicatrização.
A presença na saliva de proteínas envolvidas na coagulação/fibrinólise mostra que este fluído biológico pode constituir um possível meio auxiliar para o diagnóstico da patologia. Os resultados obtidos provam o potencial dos estudos in silico permitindo, a partir da análise do proteoma salivar, estabelecer novos alvos para futuros estudos experimentais e identificação de potenciais biomarcadores salivares, visando a intervenção terapêutica, clínica ou de diagnóstico da DMT2.
With the development of biomedical research and new Proteomics methodologies, it was possible to identify all the proteins found in individual cells, tissues and organs and link the changes of these proteins with some pathologies, including the presence, absence, post-translational modifications or expressed quantity. To analyze the large number of proteins identified in proteomes is necessary the use of bioinformatic tools to be able to integrate the information obtained and compare with information available at different databases. These approaches are nowadays a decisive contribution to the clarification of molecular and pathophysiological mechanisms. Type 2 Diabetes mellitus (T2DM) is a prevalent disease of multifactorial etiology with important implications in the oral cavity, mainly by the increased difficulties in wound healing in diabetic patients. With tese characteristics it becomes a good study model for Medic Bioinformatics application to Dental Medicine. The present work is dedicated to the analysis of the salivary proteome resulting from T2DM to verify the presence in saliva, of modified proteins involved in blood clotting and fibrinolysis, two cellular events that are crucial to the healing process. This salivary proteome analysis is particularly relevant because, nowadays, there are no published studies about the participation of salivary proteins that justifies the hypercoagulation and hipofibrinolysis occurring in T2DM. The study of T2DM salivary proteome allowed the identification of two major inhibitors of serine proteases, alpha-1-antitrypsin (SERPINA1) and alpha-2- macroglobulin (A2M), modified in T2DM. As these inhibitors play a crucial regulatory role in coagulation/fibrinolysis being both present in altered quantities in T2DM possibly causing poor wound healing. The presence, in saliva, of proteins involved in coagulation/fibrinolysis shows that this biological fluid may be a diagnosis aid. The results obtained show the potential of in silico studies of the salivary proteome, to provide new targets for future experimental studies and a possible identification of salivary biomarkers, aiming at the therapeutical, clinical or diagnostic intervention in T2DM.
With the development of biomedical research and new Proteomics methodologies, it was possible to identify all the proteins found in individual cells, tissues and organs and link the changes of these proteins with some pathologies, including the presence, absence, post-translational modifications or expressed quantity. To analyze the large number of proteins identified in proteomes is necessary the use of bioinformatic tools to be able to integrate the information obtained and compare with information available at different databases. These approaches are nowadays a decisive contribution to the clarification of molecular and pathophysiological mechanisms. Type 2 Diabetes mellitus (T2DM) is a prevalent disease of multifactorial etiology with important implications in the oral cavity, mainly by the increased difficulties in wound healing in diabetic patients. With tese characteristics it becomes a good study model for Medic Bioinformatics application to Dental Medicine. The present work is dedicated to the analysis of the salivary proteome resulting from T2DM to verify the presence in saliva, of modified proteins involved in blood clotting and fibrinolysis, two cellular events that are crucial to the healing process. This salivary proteome analysis is particularly relevant because, nowadays, there are no published studies about the participation of salivary proteins that justifies the hypercoagulation and hipofibrinolysis occurring in T2DM. The study of T2DM salivary proteome allowed the identification of two major inhibitors of serine proteases, alpha-1-antitrypsin (SERPINA1) and alpha-2- macroglobulin (A2M), modified in T2DM. As these inhibitors play a crucial regulatory role in coagulation/fibrinolysis being both present in altered quantities in T2DM possibly causing poor wound healing. The presence, in saliva, of proteins involved in coagulation/fibrinolysis shows that this biological fluid may be a diagnosis aid. The results obtained show the potential of in silico studies of the salivary proteome, to provide new targets for future experimental studies and a possible identification of salivary biomarkers, aiming at the therapeutical, clinical or diagnostic intervention in T2DM.
Description
Keywords
Diabetes Mellitus tipo 2 Proteoma salivar Bioinformática Coagulação sanguínea Fibrinólise SERPINA1 A2M Type 2 Diabetes mellitus Salivary proteome Bioinformatics Blood clotting Fibrinolysis