Endothelial cell hypoxia associated proteins are cell and stress specific.
Vascular endothelial cells (EC) are one of the initial cells exposed to decreases in blood oxygen tension. Bovine EC respond not only by altering secretion of vasoactive, mitogenic, and thrombogenic substances, but also by developing adaptive mechanisms in order to survive acute and chronic hypoxic exposures. EC exposed to hypoxia in vitro upregulate a unique set of stress proteins of Mr 34, 36, 39, 47, and 56 kD. Previous studies have shown that these proteins are cell associated, upregulated in a time and oxygen-concentration dependent manner, and are distinct from heat shock (HSPs) and glucose-regulated proteins (GRPs). To further characterize these hypoxia-associated proteins (HAPs), we investigated their upregulation in human EC from various vascular beds and compared this to possible HAP upregulation in other cell types. Human aortic, pulmonary artery, and microvascular EC upregulated the same set of proteins in response to hypoxia. In comparison, neither lung fibroblasts, pulmonary artery smooth muscle cells, pulmonary alveolar type II cells, nor renal tubular epithelial cells upregulated proteins of these Mr. Instead, most of these cell types induced synthesis of proteins of Mrs corresponding to either HSPs, GRPs, or both. Further studies demonstrated that exposure of EC to related stresses such as cyanide, 2-deoxyglucose, hydrogen peroxide, dithiothreitol, and glucose deprivation did not cause upregulation of HAPs. Evaluation of cellular damage during hypoxia using phase-contrast microscopy, trypan blue exclusion, chromium release, and adherent cell counts showed that EC survived longer with less damage than any of the above cell types. The induction of HAPs, and the lack of induction of HSPs or GRPs, by EC in response to hypoxia may be related to their unique ability to tolerate hypoxia for prolonged periods.
Graven
K K
KK
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
Zimmerman
L H
LH
Dickson
E W
EW
Weinhouse
G L
GL
Farber
H W
HW
D000328:Adult; D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008875:Middle Aged; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism*; D051381:Rats
D006360:Heat-Shock Proteins; D010100:Oxygen