A Leucine-Rich Diet Modulates the Tumor-Induced Down-Regulation of the MAPK/ERK and PI3K/Akt/mTOR Signaling Pathways and Maintains the Expression of the Ubiquitin-Proteasome Pathway in the Placental Tissue of NMRI Mice

Autor(es)

Viana, Lais Rosa ^[1] ; Cintra Gomes-Marcondes, Maria Cristina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Lab Nutr & Canc, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOLOGY OF REPRODUCTION; v. 92, n. 2 FEB 1 2015.
• Citações Web of Science: 6

Resumo

Placental tissue injury is concomitant with tumor development. We investigated tumor-driven placental damage by tracing certain steps of the protein synthesis and degradation pathways under leucine-rich diet supplementation in MAC16 tumor-bearing mice. Cell signaling and ubiquitin-proteasome pathways were assessed in the placental tissues of pregnant mice, which were distributed into three groups on a control diet (pregnant control, tumor-bearing pregnant, and pregnant injected with MAC-ascitic fluid) and three other groups on a leucine-rich diet (pregnant, tumor-bearing pregnant, and pregnant injected with MAC-ascitic fluid). MAC tumor growth down-regulated the cell-signaling pathways of the placental tissue and decreased the levels of IRS-1, Akt/PKB, Erk/MAPK, mTOR, p70S6K, STAT3, and STAT6 phosphorylated proteins, as assessed by the multiplex Millipore Luminex assay. Leucine supplementation maintained the levels of these proteins within the established cell-signaling pathways. In the tumor-bearing group (MAC) only, the placental tissue showed increased PC5 mRNA expression, as assessed by quantitative RT-PCR, decreased 19S and 20S protein expression, as assessed by Western blot analysis, and decreased placental tyrosine levels, likely reflecting upregulation of the ubiquitin-proteasome pathway. Similar effects were found in the pregnant injected with MAC-ascitic fluid group, confirming that the effects of the tumor were mimicked by MAC-ascitic fluid injection. Although tumor progression occurred, the degradation pathway-related protein levels were modulated under leucine-supplementation conditions. In conclusion, tumor evolution reduced the protein expression of the cell-signaling pathway associated with elevated protein degradation, thereby jeopardizing placental activity. Under the leucine-rich diet, the impact of cancer on placental function could be minimized by improving the cell-signaling activity and reducing the proteolytic process. (AU)

• Processo FAPESP: 12/06955-0 - Avaliação do perfil metabolômico, proteômico, das vias de proliferação celular e apoptose do câncer sob influência dos hormônios da gravidez em ratas submetidas à dieta rica em leucina
• Beneficiário: Laís Rosa Viana
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/00209-9 - Nutrição e câncer estudo das alterações metabólicas e moleculares do metabolismo protéico no câncer-caquexia, moduladas pela suplementação nutricional com leucina, no crescimento, desenvolvimento e gravidez
• Beneficiário: Maria Cristina Cintra Gomes Marcondes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/11982-3 - Avaliação do perfil de aminoácidos fetal e materno e atividade placentária em camundongas NMRI portadoras do adenocarcinoma de cólon (MAC16)
• Beneficiário: Laís Rosa Viana
• Modalidade de apoio: Bolsas no Brasil - Mestrado