Effect of Oxygen on Growth of Cultured Myocardial Cells
The present study was designed to explore the effects of environmental oxygen as a possible regulator of cardiac cell division and growth. Trypsindispersed heart cells from the ventricles of chick embryos 8 to 12 days old were grown in culture at 37°C in a nutrient medium (NCI) with 10% fetal calf serum. They were exposed to constant 5% CO2 gas environments in which the percent of O2 was varied. Net protein synthesis increased progressively as O2 was reduced from 80% to 2 to 5%. After the first 24 hours, little further protein synthesis occurred in plates grown in 80% O2. The rates of cellular incorporation of 14C-amino acids and uridine-2-14C increased progressively as the fraction of O2 was reduced. In cells grown at 80% O2, incorporation of uridine-2-14C into RNA was impaired before that of 14C-amino acid into protein. After actinomycin-D (5 µg/ml) (which quickly halted uridine incorporation into the rapidly labeled fraction of RNA), the rate of incorporation of 14C-amino acid into protein declined exponentially. This allowed for calculation of the half-life of messenger RNA (mRNA), which was the same for cells grown at 80% O2 as for cells grown at 20% O2; increased degradation of mRNA at higher Po2 is thus ruled out. Decreased O2 tension results in increased rates of cell division and protein synthesis in vitro. The molecular site of action appears to be at or before RNA readout from DNA.
- Received July 28, 1970.
- Accepted December 11, 1970.
- © 1971 American Heart Association, Inc.