• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.5.2022.tde-02052022-082927
Document
Author
Full name
Paulo Cesar Gonçalves Pereira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2021
Supervisor
Committee
Carvalho, Luciani Renata Silveira de (President)
Ferreira, Vinícius Guimarães
Tashima, Alexandre Keiji
Carvalho, Valdemir Melechco
Title in Portuguese
Estudo proteômico em saliva de pacientes adultos portadores de hipopituitarismo congênito em busca de biomarcadores que reflitam a deficiência de GH e a sua reposição
Keywords in Portuguese
Espectrometria de massas
Hipopituitarismo
Hormônio de crescimento
Proteínas e peptídeos salivares
Proteômica
Terapia de reposição hormonal
Abstract in Portuguese
Objetivo: Identificar as proteínas salivares mais relevantes que representam tanto o estado de deficiência de GH quanto a substituição de rhGh por pacientes com deficiência de GH. Metodologia: A saliva foi coletada de pacientes com deficiência de GH e controles saudáveis. A extração das proteínas salivares foi realizada com solventes orgânicos. As proteínas extraídas foram quantificadas e digeridas com tripsina e, em seguida, foi realizada a análise espectrométrica com nanoUPLC-MS (Q-TOF). As proteínas foram identificadas e a análise estatística multivariada foi utilizada para identificar as proteínas mais relevantes nos grupos. A análise ontogenética também foi realizada. Resultados: As análises de PCA foram compatíveis em todas as análises (pacientes com deficiência de GH sem rhGH versus controles saudáveis, pacientes com deficiência de GH em substituição com rhGH versus controles saudáveis e pacientes com deficiência de GH sem rhGH versus pacientes com rhGH), mas a separação foi nítida no PLS-DA. No estudo entre pacientes com deficiência de GH sem uso de rhGH versus controles saudáveis, as proteínas mais relevantes foram HSP90AA1 e HSP90AB1 (ambas com maior ênfase nos controles), chaperonas estas com inúmeras funções orgânicas. No estudo entre pacientes com deficiência de GH em reposição com rhGH versus controles saudáveis, a proteína proeminente foi a PKM (maior relevância nos controles), que está intrinsecamente envolvida com a glicólise. E no estudo entre pacientes com deficiência de GH sem rhGH versus pacientes em uso de rhGH, a proteína em destaque foi a HIST1H2BL (maior concentração nos que não usam rhGH), envolvida em processos de divisão celular. Conclusão: As proteínas identificadas demonstram o perfil de cada grupo avaliado, sendo estas marcadores da deficiência de GH (HSP90AA1 e HSP90AB1) e da reposição com rhGH (PKM e HIST1H2BL). Este estudo abre portas para o desenvolvimento de uma avaliação ou mesmo um teste para um melhor diagnóstico da deficiência de GH e avaliação da reposição de rhGH por pacientes com deficiência de GH
Title in English
Proteomic study in saliva of adult patients with congenital hypopituitarism aiming to find biomarkers that reflect GH deficiency and its replacement
Keywords in English
Growth hormone
Hormone replacement therapy
Hypopituitarism
Mass spectometry
Proteomics
Salivary proteins and peptides
Abstract in English
ABSTRACT: Objective: To identify the most relevant salivary proteins that represent as the state of GH deficiency as the replacement of rhGh by patients with GH deficiency. Methodology: Saliva was collected from GH deficient patients and healthy controls. The extraction of salivary proteins was performed with organic solvents. The extracted proteins were quantified and digested with trypsin, and then spectrometric analysis with nanoUPLC-MS (Q-TOF) was performed. Proteins were identified and multivariate statistical analysis was used to identify the most relevant proteins in the groups. Ontogenetic analysis was also performed. Results: PCA analyzes were compatible in all analyzes (GH-deficient patients without rhGH versus healthy controls, patients with GH deficiency in place of rhGH versus healthy controls, and patients with GH deficiency without rhGH versus patients with rhGH), but the separation was sharp on the PLS-DA. In the study among patients with GH deficiency without using rhGH versus healthy controls, the most relevant proteins were HSP90AA1 and HSP90AB1 (both with greater emphasis on controls), which chaperones have numerous organic functions. In the study of GH-deficient patients undergoing rhGH replacement versus healthy controls, the prominent protein was PKM (higher relevance in controls), which is intrinsically involved in glycolysis. And in the study between patients with GH deficiency without rhGH versus patients using rhGH, the highlighted protein was HIST1H2BL (higher concentration in those not using rhGH), involved in cell division processes. Conclusion: The identified proteins demonstrate the profile of each group evaluated, these being markers of GH deficiency (HSP90AA1 and HSP90AB1) and replacement with rhGH (PKM and HIST1H2BL). This study opens the door for the development of an assessment or even a test for a better diagnosis of GH deficiency and evaluation of rhGH replacement by patients with GH deficiency
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2022-05-02
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2024. All rights reserved.