Graven K K, Farber H W
The Pulmonary Center, Boston University School of Medicine, Massachusetts, USA.
J Lab Clin Med. 1998 Dec;132(6):456-63. doi: 10.1016/s0022-2143(98)90122-6.
The vascular endothelium is an important mediator of vascular tone, inflammatory-immune reactions, vascular permeability, angiogenesis, and hemostasis. Endothelial functions may be altered by changes in the local cellular environment, particularly changes in oxygen tension. The mechanisms by which endothelial cells (ECs) respond and adapt to hypoxia are unknown; however, the EC is one of the more hypoxia-tolerant mammalian cell types. Cultured ECs exposed to hypoxia up-regulate a set of stress proteins, termed hypoxia-associated proteins (HAPs), that are distinct from the classically described stress proteins induced by heat shock (heat-shock proteins, HSPs) or glucose deprivation (glucose-regulated proteins, GRPs). Two of these proteins have been identified as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and non-neuronal enolase (NNE). GAPDH expression during hypoxia is regulated primarily at the level of transcription, while the mechanism of NNE mRNA accumulation remains unclear. GAPDH, NNE, and the other HAPs are up-regulated by transitional metals and deferoxamine; however, unlike the situation with other hypoxia-regulated proteins such as erythropoietin, the up-regulation of GAPDH, NNE, and the other HAPs by hypoxia is not inhibited by carbon monoxide. Subcellular fractionation of hypoxic EC has shown that GAPDH and NNE are up-regulated in the cytoplasmic fraction as would be expected for a glycolytic enzyme; however, a protein corresponding to GAPDH is also up-regulated in the nuclear fraction. This suggests that GAPDH and perhaps NNE have functions aside from their catalytic function in glycolysis. It is unknown whether the up-regulation of GAPDH, NNE, and the other HAPs in ECs is related to the relative ability of ECs to adapt to hypoxia; however, other more-hypoxia-sensitive cells do not up-regulate HAPs.
血管内皮是血管张力、炎症免疫反应、血管通透性、血管生成和止血的重要调节因子。内皮功能可能会因局部细胞环境的变化而改变，尤其是氧张力的变化。内皮细胞（ECs）对缺氧作出反应并适应的机制尚不清楚；然而，内皮细胞是对缺氧耐受性较强的哺乳动物细胞类型之一。暴露于缺氧环境的培养内皮细胞会上调一组应激蛋白，称为缺氧相关蛋白（HAPs），这些蛋白不同于经典描述的由热休克（热休克蛋白，HSPs）或葡萄糖剥夺（葡萄糖调节蛋白，GRPs）诱导的应激蛋白。其中两种蛋白已被鉴定为糖酵解酶甘油醛-3-磷酸脱氢酶（GAPDH）和非神经元烯醇化酶（NNE）。缺氧期间GAPDH的表达主要在转录水平上受到调节，而NNE mRNA积累的机制仍不清楚。GAPDH、NNE和其他HAPs可被过渡金属和去铁胺上调；然而，与其他缺氧调节蛋白如促红细胞生成素的情况不同，一氧化碳不会抑制缺氧对GAPDH、NNE和其他HAPs的上调作用。缺氧内皮细胞的亚细胞分级分离显示，GAPDH和NNE在细胞质部分上调，这与糖酵解酶的预期情况一致；然而，与GAPDH相对应的一种蛋白在细胞核部分也上调。这表明GAPDH，也许还有NNE，除了在糖酵解中的催化功能外还有其他功能。目前尚不清楚内皮细胞中GAPDH、NNE和其他HAPs的上调是否与内皮细胞适应缺氧的相对能力有关；然而，其他对缺氧更敏感的细胞不会上调HAPs。
