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Doctoral Thesis
DOI
10.11606/T.42.2013.tde-17062014-102412
Document
Author
Full name
Lívia de Lucca Camargo
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2013
Supervisor
Committee
Lopes, Lucia Rossetti (President)
Brandes, Ralf
Chaves, Maria Luiza Morais Barreto de
Kowaltowski, Alicia Juliana
Rossoni, Luciana Venturini
Title in Portuguese
Papel da proteína dissulfeto isomerase na sinalização redox em células endoteliais e musculares lisas vasculares.
Keywords in Portuguese
Angiotensina II
Células endoteliais
Células musculares
Pressão sanguínea
Sistema cardiovascular (fisiopatologia)
Abstract in Portuguese
A proteína dissulfeto isomerase (PDI) tem ganhado destaque em processos de sinalização celular. O objetivo deste trabalho foi investigar o papel da PDI na sinalização redox induzida por TNF-a em células endoteliais e por Angiotensina II (Ang II) em células musculares lisas vasculares (CMLV). Em cultura de células endoteliais isoladas da veia umbilical humana (HUVECs) os dados demonstraram que a PDI e a ERp46 regulam especificamente a fosforilação da ERK 1/2 induzida por TNF-a, possivelmente via alterações redox sobre a GTPase Ras e participa da angiogenese induzida por TNF-a. Em CMLV de artérias de resistência, os dados sugerem a participação da PDI na contração induzida por Ang II, bem como na disfunção vascular associada à hipertensão arterial, através da regulação da expressão e atividade da Nox1. Desta forma, podemos concluir que a PDI apresenta um papel na regulação da sinalização redox induzida por TNF-a e Ang II em células endoteliais e CMLV, respectivamente. Tais resultados apontam para um novo papel da PDI na fisiopatologia do sistema cardiovascular.
Title in English
Role of protein disulfide isomerase in redox signaling in endothelial and vascular smooth muscle cells.
Keywords in English
Angiotensin II
Blood pressure
Cardiovascular system (pathophysiology)
Endothelial cells
Muscle cells
Abstract in English
Protein disulfide isomerase (PDI), an oxidoreductase of endoplasmic reticulum, has emerged as a key player in cell signaling. The aim of the present study was to investigate the role of PDI in redox signaling induced by TNF-a in endothelial cells and by Angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs). In human umbilical vein endothelial cells (HUVECs) ERp46 or PDI inhibition reduced specifically TNF-a-induced ERK1/2 phosphorylation, possibly via redox modifications in Ras GTPase and TNF-a-induced angiogenesis. In VSMCs from resistance arteries, our results suggest that PDI positively regulates Nox1 dependent signaling and expression in VSMCs from resistance arteries and could be a new player in the oxidative stress and vascular dysfunction observed in hypertension. Altogether, the results provide evidence for a role for PDI in cardiovascular pathophysiology.
 
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Publishing Date
2014-06-17
 
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