Teodoro Rita O, O'Farrell Patrick H
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
EMBO J. 2003 Feb 3;22(3):580-7. doi: 10.1093/emboj/cdg070.
Oxygen plays a key role in energy metabolism. However, there are organisms that survive severe shortfalls in oxygen. Drosophila embryos rapidly arrest development upon severe hypoxia and recover upon restoration of oxygen, even days later. Stabilization of the normally unstable engrailed RNA and protein preserved the localized striped pattern of this embryonic patterning gene during 3 days in hypoxia. Severe hypoxia blocked expression of a heat-shock-inducible lacZ transgene. Cyanide, a metabolic poison, did not immediately block gene expression or turnover, arguing against a passive response to energy limitation. In contrast, nitric oxide, a putative hypoxia signal, induced a reversible arrest of development, gene expression and turnover. Reciprocally, a nitric oxide scavenger allowed continued gene expression and turnover during hypoxia, but it reduced hypoxia tolerance. We suggest that hypoxia-induced stasis preserves the status quo of embryonic processes and promotes survival. Our data implicate nitric oxide as a mediator of this response and provide a system in which to investigate its action.
氧气在能量代谢中起着关键作用。然而，有些生物能够在氧气严重短缺的情况下存活。果蝇胚胎在严重缺氧时会迅速停止发育，并在恢复氧气供应后恢复，即使是数天之后。在缺氧的3天里，通常不稳定的engrailed RNA和蛋白质的稳定性维持了这个胚胎模式形成基因的局部条纹模式。严重缺氧阻断了热休克诱导的lacZ转基因的表达。代谢毒物氰化物并未立即阻断基因表达或周转，这表明并非对能量限制的被动反应。相反，一氧化氮作为一种假定的缺氧信号，会诱导发育、基因表达和周转的可逆性停滞。相应地，一氧化氮清除剂可使缺氧期间基因表达和周转持续进行，但会降低缺氧耐受性。我们认为，缺氧诱导的停滞维持了胚胎过程的现状并促进了存活。我们的数据表明一氧化氮是这种反应的介质，并提供了一个研究其作用的系统。
