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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2011.tde-09022012-123037
Document
Author
Full name
Luciana Paroneto Medina
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Chammas, Roger
Lepique, Ana Paula
Title in Portuguese
Modulação da morte mediada por FAS em células tipo I e tipo II.
Keywords in Portuguese
Apoptose
Imunologia celular
Mitocôndrias
Prostaglandinas
Abstract in Portuguese
O processo de morte por apoptose pode ser dividido em duas vias: intrínseca e extrínseca. A sinalização via FAS (extrínseca) pode ocorrer independente (células Tipo I) ou dependente da mitocôndria (células Tipo II). É importante considerar que: 1) Resultados prévios mostraram que doses subletais de CHX foram capazes de sensibilizar células Tipo I e Tipo II à apoptose e de converter células Tipo II em Tipo I; 2) Um dos mecanismos envolvidos pode ser o recrutamento de FAS para as "balsas lipídicas"; 3) A PGE2 ativa PKA pelo aumento de cAMP via EP2 e EP4, que fosforila ezrina, envolvida nesse processo; 4) A PGE2 pode induzir apoptose em linhagens celulares e sensibilizá-las a esse processo. Assim, formulamos a hipótese de que a PGE2 poderia, assim como a CHX, sensibilizar certas células à apoptose e converter células Tipo II em Tipo I. Esse efeito não foi observado em células DO11.10 nas quais a apoptose foi induzida por CD95L solúvel e em células Tipo I e Tipo II, nas quais a apoptose foi induzida pelo anticorpo agonista anti-FAS.
Title in English
Modulation of FAS-mediated death in type I and type II cells.
Keywords in English
Apoptosis
Cellular immunology
Mitochondria
Prostaglandins
Abstract in English
The death process by apoptosis can be divided into two pathways: intrinsic and extrinsic. The signaling by FAS (extrinsic) may occur in a mitochondrial independent (Type I cells) or dependent (Type II cells) manner. It is important to consider that: 1) Previous results demonstrated that sub-lethal doses of CHX were able to sensitize type I and type II cells to apoptosis and to convert type II cells into type I; 2) One of the mechanisms involved can be FAS recruitment to "lipid rafts"; 3) PGE2 activates PKA by increasing cAMP via EP2 and EP4, which phosphorylates of Ezrin, involved in this process; 4) PGE2 can induces apoptosis in cell lines and can to sensitize them to this process. So, we hypothesized that PGE2 could, similarly to CHX, sensitize certain cells to apoptosis and convert type II cells into type I. This effect was not observed in DO11.10 cells in which apoptosis was induced by soluble CD95L and in type I and type II cells, in which apoptosis was induced by agonist anti-FAS antibody.
 
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Publishing Date
2012-03-14
 
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