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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2015.tde-26082015-120432
Document
Author
Full name
Diogo Antonio Alves de Vasconcelos
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Curi, Rui (President)
Carvalho, Carla Roberta de Oliveira
Martins, Anna Karenina Azevedo
Santos, Camilo de Lellis
Souza, Heraldo Possolo de
Title in Portuguese
Efeitos da L-glutamina sobre a atividade das vias de sinalização da síntese e degradação de proteínas no músculo esquelético de camundongos e no conteúdo intracelular de aminoácidos em miotubos cultivados.
Keywords in Portuguese
4E-BP1
Akt
Balanço proteico muscular
Dexametasona
eIF2α
Insulina
Isoleucina
Leucina
Massa muscular esquelética
Metabolismo de aminoácidos
S6K
Valina
Abstract in Portuguese
Investigou-se os efeitos da L-glutamina (1g/kg de massa corpórea) em camundongos jejuados por 24 horas. A L-glutamina atenuou a perda de massa muscular e a diminuição da área das fibras musculares esqueléticas causadas pelo jejum via Akt-mTOR. No sóleo, a L-glutamina estimulou a Akt (início da via), e no EDL ativou a S6 (final da via). Investigou-se também os efeitos da L-glutamina em miotubos (C2C12) cultivados por 48 horas. A diminuição de L-glutamina no meio (de 2 para zero mM) causou balanço proteico negativo e aumento do conteúdo dos aminoácidos livres, exceto dos produtos da glutaminólise, indicando estimulação de proteólise. O aumento de L-glutamina no meio (de 2 para 8 e 16 mM) não alterou o conteúdo intracelular de proteínas e dos aminoácidos livres. Na presença de 2 mM de glutamina no meio, a insulina teve efeito positivo no balanço proteico via Akt/mTOR/S6K, estimulando a S6K. Na ausência de glutamina, houve maior fosforilação de eIF2α estimulada por dexametasona e portanto menor síntese proteica.
Title in English
Effects of L-gultamine on the signaling pathways of protein synthesis and degradation in skeletal muscle and intracellular free aminoacids contente in cultured miotubes.
Keywords in English
4E-BP1
Akt
Amino acid metabolismo
Dexamethasone
eIF2α
Insulin
Isoleucine
Leucine
Protein turnover of skeletal muscle
S6K
Skeletal muscle mass
Valine
Abstract in English
We investigated the effects of L-glutamine (1g/kg of body mass) on 24 h fasted mice. L-Glutamine attenuated the loss of muscle mass and the reduction of the skeletal muscle fibers area caused by fasting. This attenuation occurred via Akt-mTOR, however, glutamine stimulated Akt (upstream) in the soleus, whereas it activated S6 (dowstream) in EDL. The effects of L-glutamine on myotubes (C2C12) cultured for 48 hours were also examined. The reduction of L-glutamine in the medium (from 2 to zero mM) decreased protein content and increased contents of all amino acids, except products of glutaminolysis, indicating stimulation of proteolysis. The increased L-glutamine levels in the medium (from 2 to 8 and 16 mM) did not change the intracellular contents of protein and free amino acids. In the presence of 2 mM glutamine, insulin had a positive effect on total protein content through Akt/mTOR/S6K pathway, stimulating S6K. In turn, in the absence of L-glutamine, there was increased eIF2α phosphorylation stimulated by dexamethasone and thus less protein synthesis.
 
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Publishing Date
2015-08-28
 
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