Endothelial cells downregulate expression of the 70 kDa heat shock proteinduring 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 invest igated the effect of hypoxia on Hsp70 in human microvascular endothelial HM EC-1 cells, Reduction of pO(2) to 2.5% of normal for 20 h stimulated lactat e production and the activity of glycolytic enzymes, This metabolic adaptat ion to hypoxia was accompanied by a remarkable reduction of Hsp70 on the pr otein level and on the mRNA level, Approximately 12 h after the hypoxic per iod Hsp70 expression reached pre-hypoxia levels again. Since ECs are adapte d to the low oxygen tension of the vasculature they are confronted with a s upraphysiological oxygen level during in vitro culture. We suppose that the high Hsp70 under these conditions reflects a stress response which disappe ars at the more physiological reduced oxygen tension during hypoxia. (C) 20 00 Academic Press.