Effects of hypoxia on the oxygen-dependent metabolism of prostaglandins and adenosine in liver cells.
In this study, the capacity of hepatocytes to degrade prostaglandins diminished if the partial oxygen pressure dropped below 5%. This decrease was accompanied by an increased lactate/pyruvate ratio, a decrease in fatty acid oxidation and a drop in the ATP level. The degradation of exogenous adenosine increased with decreasing oxygen tension. At a partial oxygen pressure below 10%, the conversion of uric acid to allantoin, the final catabolite of adenosine in the rat, was strongly inhibited, resulting in the accumulation of uric acid in the medium. A good correlation was observed between the partial oxygen pressure, the oxidation of uric acid to allantoin and the degradation of prostaglandins D2 and E2, suggesting a peroxisomal pathway of hepatic prostaglandin oxidation. Subcellular fractionation of liver homogenates revealed peroxisomes as the site of degradation of prostaglandins D2 and E2 augmented by cytosolic components. The similarity of the degradation products found in the cell-free system, in hepatocytes and in the perfused liver further supports a peroxisomal degradation of prostaglandins in vivo. Stimulated liver macrophages (Kupffer cells) produced the same amount and pattern of eicosanoids at 1% and 21% O2. Even the formation of superoxide remained unaffected down to a partial pressure of 1%. At partial O2 pressures below 1%, the production of prostaglandins and superoxide became strongly inhibited. These results indicate that essential oxygenation reactions in activated Kupffer cells, including prostaglandin synthesis, possess high affinities to oxygen, while the peroxisomal pathway of prostaglandin oxidation in hepatocytes is sensitive to an O2 tension as low as 5%.
Tran-Thi
T A
TA
Biochemisches Institut der Albert-Ludwigs-Universität, Freiburg i. Br., Germany.
Holstege
A
A
Decker
K
K
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D000860:Hypoxia / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D015230:Prostaglandin D2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism
D011453:Prostaglandins; D013481:Superoxides; D000241:Adenosine; D015230:Prostaglandin D2; D010100:Oxygen