Tissue sites of degradation of apoprotein A-I in the rat.
The tissue sites of degradation of apoprotein A-I were determined in the rat in vivo using a newly developed tracer of protein catabolism, an adduct of 125I-tyramine and cellobiose. This methodology takes advantage of the fact that when a protein labeled with 125I-tyramine-cellobiose is taken up and degraded, the radiolabeled ligand remains trapped intracellularly. Thus, radio-iodine accumulation in a tissue acts as a cumulative measure of protein degradation in that tissue. In the present studies, apoprotein AI (apo-A-I) was labeled with tyramine-cellobiose (TC). The TC-labeled apo-A-I was then reassociated with high density lipoprotein (HDL) in vivo by injection into donor animals. After 30 min, serum from donor animals was recovered and then injected into recipient rats. TC-labeled apo-A-I in the donor serum was shown to be exclusively associated with HDL. The fractional catabolic rate of 125I-TC-apo-A-I was not significantly different from that of conventionally labeled apo-A-I. The kidney was the major site of degradation, accounting for 39% of the total. The liver was responsible for 26% of apo-A-I catabolism, 96% of which occurred in hepatocytes. The kidney was also the most active organ of catabolism/g of wet weight. The tissues next most active/g of wet weight were ovary and adrenal, a finding that is compatible with a special role of HDL in the rat for delivery of cholesterol for steroidogenesis. Immunofluorescence studies of frozen sections of rat kidney demonstrated the presence of apo-A-I on the brush-border and in apical granules of proximal tubule epithelial cells. Preliminary studies using HDL labeled both with 125I-TC-apo-A-I and [3H]cholesteryl ethers again demonstrated high rates of renal uptake of apo-A-I but less than 1% of total ether uptake. It is postulated that the high activity of kidney was not due to uptake of intact HDL particles, but rather, due to glomerular filtration and tubular reabsorption of free apo-A-I.
D000818:Animals; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000097:blood / Q000378:metabolism*; D005260:Female; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D007457:Iodine Radioisotopes; D008075:Lipoproteins, HDL