Department of Pediatrics, Division of Neonatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Proc Am Thorac Soc. 2011 Nov;8(6):477-84. doi: 10.1513/pats.201103-032MW.
Lung cells experience hypoxia during development, during travel to high altitude, and in acute and chronic lung diseases. The functional responses evoked by hypoxia are diverse and generally act to protect the cells from hypoxic injury, although some lung cell responses are counterproductive because they degrade normal function of the organ. The cellular O(2) sensor responsible for many of these responses involves the mitochondrial electron transport chain. Under hypoxic conditions, increased release of reactive oxygen species from the inner mitochondrial membrane to the intermembrane space leads to the activation of transcription factors, including hypoxia-inducible factor, activation of hypoxic pulmonary vasoconstriction, activation of AMP-dependent protein kinase, and internalization of the membrane Na,K-ATPase from the basolateral membrane of alveolar epithelial cells. Although the specific targets of reactive oxygen species signals are not fully understood, this signaling pathway is critical for development and for normal lung responses in the newborn and the mature lung.
在发育过程中、高原旅行时以及在急性和慢性肺部疾病中，肺细胞会经历缺氧。缺氧引起的功能反应多种多样，通常能保护细胞免受缺氧损伤，但有些肺细胞的反应适得其反，因为它们破坏了器官的正常功能。许多此类反应所涉及的细胞 O(2)感受器涉及线粒体电子传递链。在缺氧条件下，线粒体内膜向膜间空间释放的活性氧增加，导致转录因子的激活，包括缺氧诱导因子、低氧性肺血管收缩的激活、AMP 依赖的蛋白激酶的激活以及肺泡上皮细胞基底外侧膜上的膜 Na,K-ATP 酶的内化。尽管活性氧信号的具体靶标尚不完全清楚，但这种信号通路对于发育以及新生儿和成熟肺的正常肺部反应至关重要。
