Proteolysis in the rat lung: hypoxia and evidence for an inhibitor of proteolysis.
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.
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002250:Carbon Radioisotopes; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007552:Isotonic Solutions / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008168:Lung / Q000032:analysis / Q000378:metabolism*; D008297:Male; D010100:Oxygen / Q000008:administration & dosage; D010477:Perfusion; D011480:Protease Inhibitors / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D000077331:Ringer's Solution
D002250:Carbon Radioisotopes; D006454:Hemoglobins; D007552:Isotonic Solutions; D007773:Lactates; D011480:Protease Inhibitors; D011506:Proteins; D019344:Lactic Acid; D000077331:Ringer's Solution; D000255:Adenosine Triphosphate; D010100:Oxygen