Secretion of lipoproteins, apolipoprotein A-I and apolipoprotein E by isolated and perfused liver of rat with experimental nephrotic syndrome

Abstract

Nephrotic syndrome induced in the rat by the administration of puromycin aminonucleoside is accompanied by a hyperlipoproteinemia characterized by an elevation of all plasma lipoproteins, particularly of VLDL (1.006 g/ml) and HDL1 (1.050-1.090 g/ml). The increase of HDL1 is due to the accumulation of a lipoprotein species floating mainly in the density interval 1.050-1.090 g/ml, in which apolipoprotein A-I replaces apolipoprotein E as the major constituent peptide. This lipoprotein has been designated nephrotic HDL. The present study was conducted to establish whether nephrotic liver secreted more lipoproteins than the control liver and, in addition, produced a lipoprotein similar to nephrotic HDL found in plasma. Isolated livers from control and nephrotic rats were perfused with a lipoprotein-free medium for 3 h in a recirculating system. Lipoproteins were isolated by ultracentrifugation; apolipoprotein A-I and apolipoprotein E were measured in the whole perfusate at various time intervals. Nephrotic liver secreted twice as much VLDL and HDL2 and 30% more LDL and HDL1 than the control liver. This was accompanied by an increased secretion of both apolipoprotein A-I and apolipoprotein E, the levels of which were 6.5- and 2-fold, respectively, of those found in the control perfusates at the end of the perfusion. In view of the increased secretion of apolipoprotein A-I, the apolipoprotein A-I to apolipoprotein E ratio was much higher in the perfusates of nephrotic livers than in…