Proteolysis in the rat lung: hypoxia and evidence for an inhibitor of proteolysis

Abstract

We labeled proteins with [14C]phenylalanine in rats breathing air and assessed the rate of proteolysis in the isolated ventilated lung by measuring the accumulation of [14C]phenylalanine in the medium perfusing the lung. Ventilation with 0% O2 decreased the rate of proteolysis and the ATP content in the lung 60%. Medium from lungs ventilated with 0% O2, when used to perfuse lungs ventilated with 95% O2, decreased the rate of proteolysis 60% without lowering the ATP content of the lung. Correcting the pH of "used" medium or dialyzing used medium did not decrease its ability to inhibit proteolysis. Used medium from nonhypoxic lungs, or exogenous lactate (50 mM), diminished proteolysis only 20%. In a cell-free system the degradation by cathepsin D of radioactive lung proteins and radioactive hemoglobin was decreased by used medium from hypoxic lungs. We conclude that the hypoxic perfused lung releases a factor(s) that decreases the rate of proteolysis in nonhypoxic lungs and that this factor may be a protease inhibitor.

Reversible inhibition of protein synthesis in lung by halothane

“…Although the overall regulation of proteolysis in lung tissue has not been much investigated, hypoxia inhibits protein degradation in the lung (Chiang et al, 1981) and other tissues (Chua et al, 1979). In the latter case, these effects are associated with accumulation of lactate and H+ ions, products of anaerobic metabolism.…”