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Doctoral Thesis
DOI
10.11606/T.42.2015.tde-10122015-070134
Document
Author
Full name
Daniel May de Oliveira
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Câmara, Niels Olsen Saraiva (President)
Arida, Ricardo Mario
Ferrari, Merari de Fatima Ramires
Silva, Sérgio Gomes da
Torrão, Andréa da Silva
Title in Portuguese
Efeito do ácido graxo de cadeia curta, acetato, nas células da microglia ativadas por lipopolissacáride (LPS).
Keywords in Portuguese
Acetato
Ácido graxo de cadeia curta
Autofagia
Inflamação
Lipopolissacáride
Microglia
Viabilidade celular
Abstract in Portuguese
Introdução: Ácidos graxos de cadeia curta (AGCC) são compostos que contêm de 1 a 6 átomos de carbono. Estudos mostraram que possuem efeitos imunomoduladores, antiproliferativos e pró-apoptóticos, via ativação de receptores acoplados à proteína G ou via controle epigenético, agindo na histona acetil transferase (HAT) e na histona deacetilase (HDAC). O acetato é o AGCC encontrado em maiores concentrações nos cólons e no sangue, sendo também um intermediário em diversas reações metabólicas. Apesar disso, foi pouco estudado até o momento. As células da microglia são os macrófagos residentes no sistema nervoso central e desempenham importante papel em diversas doenças. Objetivo: estudar os efeitos do acetato na microglia esclarecendo seus efeitos na produção de mediadores inflamatórios e na viabilidade celular. Conclusão: O acetato estimula a produção de TNF-α e melhora a viabilidade de culturas da microglia ativadas por LPS. A melhora da viabilidade celular ocorre pela indução de autofagia. O mecanismo responsável pela indução da autofagia é epigenético, sendo completamente independente da ativação de receptores GPR.
Title in English
Effect of the short chain fatty acid, acetate, on microglial cells activated by lipopolysaccharide (LPS).
Keywords in English
Acetate
Autophagy
Cell viability
Inflammation
Lipopolysaccharide
Microglia
Short Chain Fatty Acid
Abstract in English
Introduction: short-chain fatty acids (SCFA) are compounds containing from 1 to 6 carbon atoms. Studies have shown that these compounds have immunomodulatory, anti-proliferative and pro-apoptotic effects via activation of G-protein coupled receptors or via epigenetic control acting on histone acetyl transferase (HAT) and histone deacetylase (HDAC). Acetate is the SCFA found in highest concentrations in the colon and blood. It is also an intermediate in many metabolic reactions. Nevertheless, it was little studied so far. The microglial cells are resident macrophages of the central nervous system and play an important role in several diseases. Objective: To study the effects of acetate on microglia and clarify its effects on inflammatory mediators production and cell viability. Conclusion: Acetate stimulates TNF-α production and improves cell viability of microglial cultures activated by LPS. The improved cell viability occurs by autophagy induction. The mechanism responsible for induction of autophagy is epigenetic, being completely independent of the GRP receptor activation.
 
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Release Date
2017-12-09
Publishing Date
2015-12-10
 
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