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Master's Dissertation
DOI
10.11606/D.42.2012.tde-30012013-103651
Document
Author
Full name
Camila Bonin Pinto
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Camargo, Maristela Martins de (President)
Armelin, Hugo Aguirre
Barbuto, Jose Alexandre Marzagao
Title in Portuguese
Efeito da desregulação da via UPR sobre a expressão da ciclina A1 em linfócitos B humanos.
Keywords in Portuguese
Apoptose
Ciclinas
Ciclo celular
Imunologia celular
Linfócitos B
Retículo endoplasmático
Abstract in Portuguese
A via Unfolded Protein Response (UPR) é uma via de sinalização ativada pelo estresse do Retículo endoplasmático (ER). Anteriormente descrevemos um Paciente com Imunodeficiência Comum Variável (CVID) que apresenta um atraso na ativação da via UPR associado com o acumulo de imunoglobulinas dentro do ER e uma taxa de proliferação diminuída. Nossos resultados demonstram que a ativação crônica da UPR interrompe o ciclo celular de EBV-B através da quebra da natureza cíclica da ciclina A1. Essa parada é depende da linhagem EBV-B estudada e da droga utilizada. Além disso, a ativação crônica da UPR aumenta a apoptose através da ativação do braço da PERK da via UPR. Células ex-vivo e EBV-B do Paciente P apresentaram uma taxa metabólica muito baixa e numero aumentado de células em apoptose. A deficiência da resposta do paciente P frente a ativação da via UPR parece ser somente no reconhecimento de proteínas não dobradas. Nossos resultados sugerem que a proliferação deficiente observada em diversos paciente com CVID pode ser resultado de uma ativação deficiente da via UPR.
Title in English
Effect of the deregulation of the UPR pathway in the expression of cyclin A1 in human B lymphocytes.
Keywords in English
Apoptosis
B lymphocytes
Cell cycle
Cellular immunology
Cyclins
Endoplasmic reticulum
Abstract in English
The unfolded protein response (UPR) is a signaling pathway activated by endoplasmic reticulum (ER) stress. Previously we described a patient (Patient P) with Common Variable Immunodeficiency (CVID) whose delayed activation of the UPR associates with accumulation of immunoglobulins and slower rate of proliferation. Our results showed that chronic UPR stress interrupted cell cycling of EBV-B cells through dysruption of the cyclic nature of cyclin A1. This interrption is depend of the cell type and drug. Furthermore, chronic ER stress triggered early apoptosis through activation of the PERK branch of the UPR. EBV-B and ex vivo cells from patient presented low metabolic rate and a high apoptosis rate even in the absence of ER stressors.. We noted that the deficiency of UPR pathway activation by Patient P apears to be on the recognition of unfolded proteins. Our results support the hypothesis that deficient proliferation observed in some CVID patients might be the result of deficient UPR activation.
 
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Release Date
2017-03-08
Publishing Date
2013-03-21
 
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