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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Peroxisome proliferator-activated receptor-y coactivator 1-α(PGC1α) is a metabolic regulator of intestinal epithelial cell fate
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Peroxisome proliferator-activated receptor-y coactivator 1-α(PGC1α) is a metabolic regulator of intestinal epithelial cell fate

机译：过氧化物酶体增殖物激活受体-γ共激活物1-α（PGC1α）是肠道上皮细胞命运的代谢调节剂

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摘要

Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1a) is a transcriptional coactivator able to up-regulate mito-chondrial biogenesis, respiratory capacity, oxidative phosphoryla-tion, and fatty acid p-oxidation with the final aim of providing a more efficient pathway for aerobic energy production. In the continuously renewed intestinal epithelium, proliferative cells in the crypts migrate along the villus axis and differentiate into mature enterocytes, increasing their respiratory capacity and finally undergoing apoptosis. Here we show that in the intestinal epithelial surface, PG1Iα drives mitochondrial biogenesis and respiration in the presence of reduced antioxidant enzyme activities, thus determining the accumulation of reactive oxygen species and fostering the fate of enterocytes toward apoptosis. Combining gain- and loss-of-function genetic approaches in human cells and mouse models of intestinal cancer, we present an intriguing scenario whereby PGC1α regulates enterocyte cell fate and protects against tumorigenesis.
机译：过氧化物酶体增殖物激活受体-γ共激活因子1-α（PGC1a）是一种转录共激活因子，能够上调线粒体的生物发生，呼吸能力，氧化磷酸化和脂肪酸p-氧化，最终目的是提供更多的功能。有氧能源生产的有效途径。在不断更新的肠上皮中，隐窝中的增生细胞沿绒毛轴迁移并分化为成熟的肠上皮细胞，从而增加了它们的呼吸能力并最终经历了细胞凋亡。在这里，我们显示在肠上皮表面，PG1Iα在抗氧化酶活性降低的情况下驱动线粒体的生物发生和呼吸作用，从而确定了活性氧的积累并促进了肠上皮细胞向凋亡的命运。结合人类细胞和小鼠小肠癌模型中功能获得和丧失功能的遗传方法，我们提出了一个有趣的场景，其中PGC1α调节肠上皮细胞的命运并防止肿瘤发生。

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    llenia DErrico; Lorena Salvatore; Stefania Murzilli; Giuseppe Lo Sasso; Dominga Latorre; Nicola Martelli; Anastasia V. Egorova; Roman Polishuck; Katja Madeyski-Bengtson; Christopher Lelliott; Antonio J. Vidal-Puig; Peter Seibel; Gaetano Villani; Antonio Moschetta;

  • 作者单位

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, Italy;

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, Italy;

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, Italy;

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, Italy;

    Department of Medical Biochemistry, Biology, and Physics, University of Bari, 70124 Bari,Italy;

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, Italy;

    Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy;

    Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy;

    AstraZeneca Transgenic and Comparative Genomics, AstraZeneca Research and Development, SE-43183 Moelndal, Sweden;

    Department of Biosciences, AstraZeneca Research and Development, SE-43183 Molndal, Sweden;

    Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ,United Kingdom;

    Department of Molecular Cell Therapy, Center for Biotechnology and Biomedicine, University of Leipzig, 04103 Leipzig, Germany;

    Department of Medical Biochemistry, Biology, and Physics, University of Bari, 70124 Bari,Italy;

    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy,Clinica Medica 'A. Murri,' University of Bari, 70124 Bari, ltaly;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    colon cancer; medical physiology; metabolism; mitochondria; nuclear receptors;

    机译：结肠癌;医学生理学;代谢;线粒体;核受体;

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