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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-02022018-171357
Document
Author
Full name
Vitor Felitti
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Carvalho, Carla Roberta de Oliveira (President)
Akamine, Eliana Hiromi
Caperuto, Luciana Chagas
Saad, Mario Jose Abdalla
Silva, Silvana Auxiliadora Bordin da
Title in Portuguese
DHEA reduz a apoptose e modula a resposta do retículo sarcoplasmático ao estresse celular induzidos por palmitato em miotubos L6.
Keywords in Portuguese
Ácido graxo
Apoptose
Desidroepiandrosterona
Estresse de Retículo
Músculo esquelético
Abstract in Portuguese
A desidroepierosterona (DHEA) é um hormônio esteroide produzido pelas glândula adrenal e gônadas em humanos. Diversas evidencias do efeitos anti-obesidade, antiinflamatórios e antioxidativos, além de ser precursor dos esteroides sexuais. No presente trabalho foi avaliando o efeito do DHEA sobre a citotoxicidade induzida 0,5mM de palmitato em miotubos L6, usando 2 concentrações distintas para o esteroide, uma próxima à fisiológica (10nM) e outra supra-fisiológica (100nM) por 12h. Foram avaliados parâmetros: viabilidade celular, apoptose, vias intracelulares envolvidas na apoptose, no estresse de retículo endoplasmatico e estado de estresse oxidativo. Os resultados obtidos foram, para ambas as concentrações de DHEA a redução do estresse de reticulo induzido por palmitato via Perk/eif2α/CHOP. Além disso o DHEA impediu o aumento da expressão de iNOS e de proteína nitradas induzidas por palmitato. A partir dos resultados concluímos que o DHEA, tem efeitos anti-apoptótico e regulador da UPR. Alem do DHEA ter sido eficaz na redução do estresse oxidativo.
Title in English
DHEA reduces apoptosis and modulates the response of palmitate-induced cellular stress in the sarcoplasmic reticulum of L6 myotubes.
Keywords in English
Apoptosis
Dehydroepiandrosterone
Fatty acid
Reticle stress
Skeletal muscle
Abstract in English
Dehydroepierosterone (DHEA) is a steroid hormone produced by the adrenal gland and gonads in humans. Several evidences of the antiobesity, anti-inflammatory and antioxidative effects, besides being precursor of the sexual steroids. In the present study, the effect of DHEA on the 0.5mM induced cytotoxicity of palmitate in L6 myotubes was evaluated, using 2 different concentrations for the steroid, one physiological (10nM) and one supra-physiological (100nM) for 12h. The following parameters were evaluated: cell viability, apoptosis, intracellular pathways involved in apoptosis, endoplasmic reticulum stress and oxidative stress state. The results obtained were, for both concentrations of DHEA, reduction of the stress of reticulo induced by palmitato via Perk / eif2α / CHOP. In addition, DHEA prevented increased expression of iNOS and nitrite protein induced by palmitate. From the results we conclude that DHEA has anti-apoptotic and UPR regulatory effects. In addition to DHEA, it has been effective in reducing oxidative stress.
 
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Release Date
2020-02-02
Publishing Date
2018-02-02
 
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