在微环境下低氧应急水平下的细胞代谢，干性维持、增殖和多功能性

Title:Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency

Volume: 15 Issue: 4

Author(s): M.P. De Miguel, Y. Alcaina, D. Sainz de la Maza and P. Lopez-Iglesias

Affiliation:

关键词: 癌症，发展，DNA修复，糖酵解，缺氧诱导因子，缺氧，新陈代谢，重组，活性氧，多能性

摘要: Hypoxia is defined as a reduction in oxygen supply to a tissue below physiological levels. However, physiological hypoxic conditions occur during early embryonic development; and in adult organisms, many cells such as bone marrow stem cells are located within hypoxic niches. Thus, certain processes take place in hypoxia, and recent studies highlight the relevance of hypoxia in stem cell cancer physiology. Cellular response to hypoxia depends on hypoxia-inducible factors (HIFs), which are stabilized under low oxygen conditions. In a hypoxic context, various inducible HIF alpha subunits are able to form dimers with constant beta subunits and bind the hypoxia response elements (HRE) in the genome, acting as transcription factors, inducing a wide variety of gene expression. Typically, the HIF pathway has been shown to enhance vascular endothelial growth factor (VEGF) expression, which would be responsible for angiogenesis and, therefore, re-oxygenation of the hypoxic sites. Embryonic stem cells inhibit a severely hypoxic environment, which dictates their glycolytic metabolism, whereas differentiated cells shift toward the more efficient aerobic respiration for their metabolic demands. Accordingly, low oxygen tension levels have been reported to enhance induced pluripotent stem cell (iPS) generation. HIFs have also been shown to enhance pluripotency-related gene expression, including Oct4 (Octamer-binding transcription factor 4), Nanog and Wnt. Therefore, cell metabolism might play a role in stemness maintenance, proliferation and cell reprogramming. Moreover, in the hypoxic microenvironment of cancer cells, metabolism shifts from oxidative phosphorylation to anaerobic glycolysis, a process known as the Warburg effect, which is involved in cancer progression and malignancy.

Cite this article as:

M.P. De Miguel, Y. Alcaina, D. Sainz de la Maza and P. Lopez-Iglesias , Cell Metabolism Under Microenvironmental Low Oxygen Tension Levels in Stemness, Proliferation and Pluripotency, Current Molecular Medicine 2015; 15 (4) . https://dx.doi.org/10.2174/1566524015666150505160406