首页> 外文期刊>Biology of Reproduction: Offical Journal of the Society for the Study of Reproduction >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
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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

机译:富含亮氨酸的饮食调节肿瘤诱导的MAPK / ERK和PI3K / Akt / mTOR信号通路的下调,并维持NMRI小鼠胎盘组织中泛素-蛋白酶体通路的表达。

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摘要

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.
机译:胎盘组织损伤与肿瘤发展同时发生。我们通过在MAC16荷瘤小鼠中追踪富含亮氨酸饮食饮食下蛋白质合成和降解途径的某些步骤,研究了肿瘤驱动的胎盘损伤。在妊娠小鼠的胎盘组织中评估了细胞信号传导和泛素-蛋白酶体途径,将其分为对照饮食的三个组(怀孕对照组,荷瘤孕妇和注射了MAC-腹水的孕妇)和其他三个组。富含亮氨酸的饮食(怀孕,患有肿瘤的孕妇,以及已注射MAC腹水的孕妇)。 MAC肿瘤生长下调了胎盘组织的细胞信号通路,并降低了IRS-1,Akt / PKB,Erk / MAPK,mTOR,p70S6K,STAT3和STAT6磷酸化蛋白的水平,如多重Millipore Luminex所评估的分析。补充亮氨酸可在建立的细胞信号通路内维持这些蛋白质的水平。仅在荷瘤组(MAC)中,胎盘组织显示出PC5 mRNA表达增加(通过定量RT-PCR评估),19S和20S蛋白表达(通过Western blot分析评估)降低以及胎盘酪氨酸水平降低,这可能反映了泛素-蛋白酶体途径的上调。在注射MAC-腹水组的孕妇中发现了相似的作用,证实了通过MAC-腹水注射可以模拟肿瘤的作用。尽管发生了肿瘤进展,但是在亮氨酸补充条件下调节了降解途径相关的蛋白质水平。总之,肿瘤进化降低了与蛋白质降解增加相关的细胞信号通路的蛋白质表达,从而危及胎盘的活性。在富含亮氨酸的饮食下,可以通过改善细胞信号传导活性和减少蛋白水解过程来最大程度地降低癌症对胎盘功能的影响。

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