Enhanced synthesis of specific proteins, RNA, and DNA caused by hypoxia and reoxygenation

Abstract

When Chinese Hamster ovary cells were exposed to severe hypoxia they responded with an enhanced synthesis rate of a small group of specific proteins, which we have termed the oxygen regulated proteins (ORPs). The five major ORPs had molecular weights of 33, 80,100,150, and 260 kD. ORP260 was the first ORP to be synthesized at enhanced rates after the induction of hypoxia, reaching its maximal synthesis rate after only a few hours. The other ORPs responded slower, but were being synthesized at maximal rates by 8 hr of hypoxia. Upon reoxygenation, the synthesis rates of the ORPs declined rapidly with ORP260 again responding most rapidly. They all reached control levels by 12 hr of recovery. The induction of enhanced synthesis of these proteins required a very severe degree of hypoxia. They were not seen at oxygen levels higher than 0.03%. While enhanced synthesis of the ORPs was turned on and off quickly with induction of, and recovery from hypoxia, the proteins were not degraded at high rates once synthesized. All five major ORPs have apparent half-lives in excess of 24 hr. When cells were exposed to hypoxia for 20 hr and then allowed to recover for 15 hr, a population of cells was generated that had, on average, at least twice the cell volume as aerobic control cells. These large cells also contained greater than 4C DNA content as well as enhanced amounts of RNA.