基因组完整性、干细胞与透明质酸
Genome integrity, stem cells and hyaluronan.
作者信息
Darzynkiewicz Zbigniew, Balazs Endre A
机构信息
Brander Cancer Research Institute & Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.
出版信息
Aging (Albany NY). 2012 Feb;4(2):78-88. doi: 10.18632/aging.100438.
Faithful preservation of genome integrity is the critical mission of stem cells as well as of germ cells. Reviewed are the following mechanisms involved in protecting DNA in these cells: (a) The efflux machinery that can pump out variety of genotoxins in ATP-dependent manner; (b) the mechanisms maintaining minimal metabolic activity which reduces generation of reactive oxidants, by-products of aerobic respiration; (c) the role of hypoxic niche of stem cells providing a gradient of variable oxygen tension; (d)(e) the presence of hyaluronan (HA) and HA receptors on stem cells and in the niche; (f) the role of role of HA in protecting DNA from oxidative damage; (g) the specific role of HA that may play a role protecting DNA in stem cells; (h) the interactions of HA with sperm cells and oocytes that also may shield their DNA from oxidative damage, and (e) mechanisms by which HA exerts the anti-oxidant activity. While HA has multitude of functions its anti-oxidant capabilities are often overlooked but may be of significance in preservation of integrity of stem and germ cells genome.
忠实维护基因组完整性是干细胞以及生殖细胞的关键使命。本文综述了这些细胞中涉及保护DNA的以下机制：(a) 能够以ATP依赖方式泵出多种基因毒素的外排机制；(b) 维持最低代谢活性的机制，这会减少需氧呼吸副产物活性氧化剂的产生；(c) 干细胞低氧微环境提供可变氧张力梯度的作用；(d)(e) 干细胞及其微环境中透明质酸（HA）和HA受体的存在；(f) HA在保护DNA免受氧化损伤方面的作用；(g) HA在保护干细胞中DNA方面可能发挥的特定作用；(h) HA与精子细胞和卵母细胞的相互作用，这也可能保护它们的DNA免受氧化损伤，以及(e) HA发挥抗氧化活性的机制。虽然HA有多种功能，但其抗氧化能力常常被忽视，但可能在维护干细胞和生殖细胞基因组完整性方面具有重要意义。
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