Degradation of serum amyloid A by isolated perfused rat liver.
Degradation of serum amyloid A (SAA) was studied in the isolated perfused rat liver. Radioiodinated SAA was reconstituted with high density lipoproteins (HDL) and administered to rats. Plasma was taken 1 h later, and the HDL were isolated for use as tracer. HDL-bound 125I-SAA was cleared from the plasma of intact animals at a rate similar to SAA in native human HDL. Catabolism of SAA and HDL apoproteins was studied in parallel in the perfused liver. In a 3-h perfusion, 21% of SAA was degraded in contrast to 13% of apoC-III, 7% of apoA-I, and 6% of apoA-II. SAA1 (47% in 3 h) was degraded more rapidly than SAA5 (37%) although their in vivo clearance rates were similar. Degradation of SAA was inhibited when lipoproteins were added to the perfusate. At a protein concentration of 0.15 mg/ml, low density lipoproteins inhibited 47%, HDL 62%, and SAA-rich HDL 75%. Lipid-free normal HDL (0.3 mg/ml perfusate) did not appreciably affect SAA degradation; however, delipidated SAA-rich HDL (0.3 mg of protein/ml; 0.02 mg of SAA/ml) inhibited SAA degradation by 40%. Isolated perfused mouse liver proved more effective than rat liver in degrading SAA (5.3% versus 2.8%/g of liver/h). Degradation appeared to be mediated by cell-associated enzymes since perfusate, which had been recirculated through the liver for 3 h, accounted for less than 15% of the total degradation. Partial (38%) hepatectomy did not significantly reduce apoA-I clearance but reduced that of SAA by 16%, providing additional evidence for hepatic SAA catabolism. We conclude from these studies that SAA is catabolized independently of other HDL proteins, that association with lipoproteins retards SAA clearance, and that SAA catabolism is, in part, a specific process.
D000818:Animals; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000685:Serum Amyloid A Protein; D010447:Peptide Hydrolases