Hypoxia-associated proteins.
The vascular endothelium is an important mediator of vascular tone, angiogenesis, inflammatory-immune reactions, vascular permeability, and hemostasis. Thus, it plays an important role in the pathogenesis of numerous critical care processes, including septic shock, myocardial infarction, the adult respiratory distress syndrome, and acute tubular necrosis. Endothelial functions may be altered by changes in the local cellular environment, particularly changes in PO2. The ability of endothelial cells (EC) to not only sense, but also to adapt to, acute and chronic changes in PO2 is critical to maintaining endothelial metabolic functions and, in turn, to maintaining homeostasis, particularly in the critical care setting. Recent studies have shown that the EC is one of the more hypoxia-tolerant mammalian cell types; however, the mechanisms by which ECs respond and adapt to hypoxia are unknown. Our laboratory has shown that cultured ECs exposed to hypoxia upregulate 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) or glucose deprivation (glucose-regulated proteins). We have recently identified one of these proteins as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Further studies have shown that GAPDH expression is regulated by hypoxia, primarily at the transcriptional level. Subcellular fractionation of hypoxic EC has shown that GAPDH is upregulated in the cytoplasmic fraction as would be expected with a glycolytic enzyme; however, a protein corresponding to GAPDH is also upregulated in the nuclear fraction. This suggests that the upregulation of GAPDH in EC during hypoxia is related to the potential nonglycolytic functions of this enzyme. Furthermore, the upregulation of GAPDH and the other HAPs (that have yet to be identified) may be related to the relative hypoxia tolerance of EC.
Graven
K K
KK
Pulmonary Center, Boston University School of Medicine, MA, USA.
Farber
H W
HW
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008970:Molecular Weight
D006360:Heat-Shock Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases