Enhanced synthesis of stress proteins caused by hypoxia and relation to altered cell growth and metabolism

Cultured cells maintained in very low oxygen levels alter their structure, metabolism and genetic expression. Culture conditions for cells were modified to minimise variation of nutrients and to allow normal survival levels after 24 h of hypoxic exposure. Under these hypoxic conditions, glucose consumption and lactate production rates were similar to aerobic rates until about 12 h after which the hypoxic rates increased. DNA and protein synthesis rates are continuously inhibited to about 48% or 55% of the respective aerobic rates. During this period of decreased protein synthesis, a set of proteins termed oxygen regulated proteins (ORPs), exhibits enhanced relative synthesis. The molecular weights of the five major ORPs are approximately 260, 150, 100, 80 and 33 kDa. While increased relative synthesis of oxygen regulated proteins is partly due to increased levels of mRNA which encode these proteins, the mechanism of enhanced synthesis of ORPs may be more complex.