title: Endothelial cell hypoxic stress proteins.
abstract: 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.
authors.affiliation: The Pulmonary Center, Boston University School of Medicine, Massachusetts, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Graven
authors.forename: H W
authors.initials: HW
authors.lastname: Farber
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002458:Cell Fractionation; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004790:Enzyme Induction; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis / Q000302:isolation & purification; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000096:biosynthesis / Q000302:isolation & purification; D015854:Up-Regulation
chemical_list: D006360:Heat-Shock Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010751:Phosphopyruvate Hydratase