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.
Abstract
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.
摘要
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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