Endothelial Cell Hypoxic Stress Proteins
Year: 1998
Type: article
Abstract: Among mammalian cells, vascular endothelial cells (EC) are often exposed to changes in their local environment, particularly decreases in ambient oxygen tension. Thus, tolerance to acute hypoxia and adaptation to chronic hypoxia are crucial to survival of these cells and maintenance of vascular homeostasis. Recent studies have shown that ECs are remarkably hypoxia tolerant; however, the mechanisms by which they respond and adapt to hypoxia are unknown. Our laboratory has demonstrated that cultured EC exposed to acute or chronic hypoxia upregulate a specific set of stress proteins, termed hypoxia-associated proteins (HAPs), that are distinct from other previously described stress proteins. Two of these HAPs have been identified as the glycolytic enzymes glyceraldehyde-3phosphate dehydrogenase (GAPDH) and nonneuronal enolase (NNE). Further studies have demonstrated that: (1) the expression of GAPDH, and likely NNE, is regulated by hypoxia, primarily at the transcriptional level; (2) as expected with glycolytic enzymes, GAPDH and NNE are upregulated in the cytoplasmic fraction of EC by hypoxia, and in addition, a protein corresponding to GAPDH is upregulated in the nuclear fraction of EC; (3) upregulation of the HAPs is stress-specific and occurs in all types of EC examined but does not occur in other less hypoxia-tolerant cell types (EC-specific); (4) in contrast to upregulation of other stress proteins in EC or other cell types, HAPs are not induced by unrelated cellular stresses nor are they protective against different lethal stresses; and (5) similar to other hypoxia-responsive genes, such as erythropoietin or vascular endothelial growth factor, HAPs are upregulated by transitional metals; in contrast, their upregulation is not altered by inhibitors of heme function or synthesis, protein synthesis, protein kinase C, tyrosine kinases, calcium flux, or NO production. Findings from these studies suggest that: (1) HAPs represent a specific and unique set of EC stress proteins; (2) upregulation of GAPDH and NNE in EC during hypoxia may be related to potential nonglycolytic functions of these enzymes; (3) upregulation of HAPs may be related to the relative hypoxia tolerance of EC; and (4) HAPs may be regulated differently from other hypoxia-responsive genes.
Source: CHEST Journal
Authors: Harrision W. Farber, K.K. Graven
Institution: Boston University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,160
OpenAlex ID: W2007995466