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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Leucine can modulate the expression of proteins related to protein degradation signalling under mTOR inhibition in C2C12 cells

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Author(s):
Favero-Santos, Bianca Cristine [1, 2] ; Cintra Gomes-Marcondes, Maria Cristina [1]
Total Authors: 2
Affiliation:
[1] Univ Estadual Campinas, Biol Inst, Dept Struct & Funct Biol, Lab Nutr & Canc, BR-13083862 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Biol Inst, Dept Struct & Funct Biol, Obes & Comorbid Res Ctr, Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Cellular & Molecular Biology; v. 64, n. 10, p. 73-78, 2018.
Web of Science Citations: 0
Abstract

Many metabolic syndromes lead to energetic disturbs which ends to an intense catabolic state. The branched-chain amino acid leucine shows very positive effects on muscle protein metabolism. However, it is still not clear how leucine acts improving the protein turnover. This study aimed to evaluate in vitro the effects of leucine supplementation in minimising the signalling pathway of protein degradation when mTOR was inhibited. Our studies were conducted in murine C2C12 myotubes exposed to 2mM leucine or 2mM isoleucine in control situation and compared to the inhibition of mTOR by rapamycin. Then, the expression of proteins related to protein synthesis and degradation signalling pathway was obtained by Western Blot. At this concentration, the leucine was sufficient to maintain the expression of proteins evaluated as in control situation. However, when the cells were exposed to rapamycin (80nM), leucine inhibited the expression of SMAD and FoxO3a, showing that leucine was able to modulate the degradation pathway when protein synthesis is compromised. Furthermore, leucine had no effect in modifying the expression of subunits of ubiquitin-proteasome system, showing that leucine had no direct effect in ubiquitin-proteasome system, but acted leading to the phosphorylation of SMAD and FoxO3, which inhibited the activity of transcriptional of these proteins. No similar results were observed in cells exposed to isoleucine under the same experimental protocol, likely showing that leucine has specific action over another branched-chain amino acids. In conclusion, the present study shows that leucine can modulate degradation pathways even under inhibition of mTOR by rapamycin. (AU)

FAPESP's process: 13/16115-1 - Biochemical and molecular mechanisms of cachexia. effects of Walker factor and leucine supplementation on myotube cell culture
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants
FAPESP's process: 17/02739-4 - Nutrition and cancer: study of molecular, proteomic and metabolomic aspects of experimental model of cachexia
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/13334-7 - Nutrition and cancer: metabolomic, and proteomic profile of muscle, placental, fetal, and tumor cell signaling pathways in Walker-256 tumour-bearing pregnant rats submitted to leucine nutritional supplementation
Grantee:Maria Cristina Cintra Gomes Marcondes
Support type: Regular Research Grants