Department of Neurobiology, The Scripps Research Institute, La Jolla, CA, USA.
Cell Adh Migr. 2012 Jan-Feb;6(1):49-58. doi: 10.4161/cam.19582.
In this article, I discuss the hallmarks of hypoxia in vitro and in vivo and review work showing that many types of stem cell proliferate more robustly in lowered oxygen. I then discuss recent studies showing that alterations in the levels and the types of cell and substrate adhesion molecules are a notable response to reduced O(2) levels in both cultured primary neural stem cells and brain tissues in response to hypoxia in vivo. The ability of O(2) levels to regulate adhesion molecule expression is linked to the Wnt signaling pathway, which can control and be controlled by adhesion events. The ability of O(2) levels to influence cell adhesion also has far-reaching implications for development, ischemic trauma and neural regeneration, as well as for cancer and other diseases. Finally I discuss the possibility that the fluctuations in O(2) levels known to have occurred over evolutionary time could, by influencing adhesion systems, have contributed to early symbiotic events in unicellular organisms and to the emergence of multicellularity. It is not my intention to be exhaustive in these domains, which are far from my own field of study. Rather this article is meant to provoke and stimulate thinking about molecular evolution involving O(2) sensing and signaling during eras of geologic and atmospheric change that might inform modern studies on development and disease.
在本文中，我讨论了体外和体内缺氧的特征，并回顾了表明许多类型的干细胞在低氧环境下更旺盛地增殖的工作。然后，我讨论了最近的研究表明，细胞和基质黏附分子的水平和类型的改变是对培养的原代神经干细胞和体内缺氧时脑组织中氧水平降低的显著反应。氧水平调节黏附分子表达的能力与 Wnt 信号通路有关，该通路可以控制和被黏附事件控制。氧水平影响细胞黏附的能力对发育、缺血性创伤和神经再生以及癌症和其他疾病也有深远的影响。最后，我讨论了在进化过程中已知的氧水平波动可能通过影响黏附系统，对单细胞生物中的早期共生事件以及多细胞生物的出现做出了贡献的可能性。我的目的不是在这些领域面面俱到，这些领域远非我自己的研究领域。相反，本文旨在激发和刺激对涉及氧感知和信号转导的分子进化的思考，这些思考可能为现代发育和疾病研究提供信息。
