Effects of experimentally induced nephrosis on protein synthesis in rat liver

Abstract

A nephrotic syndrome was experimentally induced in rats by a single intravenous injection of aminonucleoside of puromycin. Experimental animals were studied 8 days after the injection, at which time they exhibited marked proteinuria and hypoalbuminemia compared with control animals. The experimental animals also exhibited alterations in protein synthesis in liver as evidenced by a marked increase in the rate of albumin synthesis relative to total hepatic protein synthesis, changes in the relative concentrations of several plasma proteins, an increased protein content of plasma, an increased liver weight relative to body weight, and an increased RNA content of liver. Perfused liver preparations derived from nephrotic rats exhibited an increased release of albumin and other secretory proteins compared with control preparations. In contrast, there was no difference in the rate of synthesis of nonexported proteins between the two groups. The elevation in the relative rate of albumin synthesis was accompanied by a relative increase of the same magnitude in albumin mRNA. Furthermore, the relative amounts of several other mRNAs, including those coding for beta-fibrinogen, haptoglobin, metallothionein II, and two unidentified proteins, were increased, whereas the amount of mRNA coding for alpha 1-acid glycoprotein was decreased in livers of nephrotic rats compared to controls. These results indicate that nephrosis leads to marked alterations in the synthesis of albumin and other plasma proteins. Mechanisms responsible for these alterations include changes in the relative abundance of specific mRNAs and an increase in total cellular RNA.