Effects of hypoxia and fasting on the cytochrome concentration in intestinal epithelial villous cell mitochondria. Role of changes in the life-span of the cells.

Abstract

The effects of hypoxia in vivo (40.8 kPa barometric pressure up to 120 h) and fasting on the characteristics of intestinal epithelial villous cell mitochondria and the turnover of epithelial villous cells and mitochondria were studied in rats. Using cells and mitochondria isolated in the isotonic mannitol medium, it was found that 24-h hypoxia or fasting did not alter the mitochondrial cytochrome content, but 48-h hypoxia or fasting led to increases of 70% and 37% in the cytochrome aa3 concentration in the hypoxic and fasting animals respectively. The turnover of intestinal epithelial cells was studied by observing the labelling kinetics of the cells with 3H-thymidine and the turnover of the cell and mitochondrial proteins with (guanido-14C)-arginine or 3H-leucine. The decay in thymidine radioactivity obeyed exponential kinetics from which half-lives of 1.15, 1.31 and 1.53 days were calculated in the control, fasting and hypoxic animals respectively. The half-lives for total cellular protein were 1.31, 1.54 and 1.54 days respectively when calculated from the (guanido-14C)-arginine experiments, or 0.69, 0.75 and 0.99 days when calculated from the leucine experiments. The labelling experiments with (guanido-14C)-arginine indicated that the turnover of mitochondrial proteins in intestinal epithelial cells is the same as that of the cells themselves. Since the turnover of mitochondrial proteins in other tissues is shown to be a relatively slow process, the increase in the cytochrome concentration in the intestinal cells of the hypoxic rats must be due to the longer life of the cells, which allows for the synthesis of larger amounts of the mitochondrial components.