Endothelial cells downregulate expression of the 70 kDa heat shock protein during hypoxia.
Hsp70 is induced by hypoxia in most mammalian cell types and contributes to their ability to survive hypoxic episodes. However, little is known about Hsp70 expression in the hypoxia-tolerant endothelial cells (ECs). We investigated the effect of hypoxia on Hsp70 in human microvascular endothelial HMEC-1 cells. Reduction of pO(2) to 2.5% of normal for 20 h stimulated lactate production and the activity of glycolytic enzymes. This metabolic adaptation to hypoxia was accompanied by a remarkable reduction of Hsp70 on the protein level and on the mRNA level. Approximately 12 h after the hypoxic period Hsp70 expression reached pre-hypoxia levels again. Since ECs are adapted to the low oxygen tension of the vasculature they are confronted with a supraphysiological oxygen level during in vitro culture. We suppose that the high Hsp70 under these conditions reflects a stress response which disappears at the more physiological reduced oxygen tension during hypoxia.
Oehler
R
R
Surgical Research Laboratories, University of Vienna, Vienna, A-1090, Austria. rudolf.oehler@akh-wien.ac.at
Schmierer
B
B
Zellner
M
M
Prohaska
R
R
Roth
E
E
D001273:Atmosphere Exposure Chambers; D001798:Blood Proteins / Q000096:biosynthesis; D015152:Blotting, Northern; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004734:Energy Metabolism; D006019:Glycolysis / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008565:Membrane Proteins; D008833:Microcirculation / Q000378:metabolism; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism
D001798:Blood Proteins; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C036860:STOM protein, human; D019344:Lactic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III