REGULATION OF APOLIPOPROTEIN A-1 AND E-GENE EXPRESSION IN LIVER AND INTESTINE OF NEPHROTIC AND PAIR-FED RATS

Rats treated with puromycin aminonucleoside (PAN) developed characteri stics of the nephrotic syndrome, including albuminuria, hypoalbuminemi a and hyperlipidemia. To study the regulation of apolipoprotein (apo) A-1 and apo E gene expression in nephrotic rats, we analyzed the stead y-state levels (SSLs) of hepatic and intestinal apo A-1 and apo E mRNA using the Northern technique, and the plasma levels of high-density l ipoprotein (HDL) by biochemical methods. Male Wistar rats were treated with PAN and compared with pair-fed and untreated control rats at dif ferent stages of disease. Nephrotic rats presented with marked hypoalb uminemia and albuminuria at between 6 and 11 days after PAN treatment. During this stage of disease, plasma levels of HDL were elevated in c orrelation with an increase of both hepatic and intestinal apo A-1 mRN A. In liver of nephrotic rats, high levels of apo A-1 mRNA together wi th low levels of apo E mRNA caused an increase in the ratio of apo A-1 /apo E mRNA, reaching a maximum 6 days after treatment. Apo E mRNA was barely detected in small intestine of pair-fed controls and PAN-treat ed rats. However, contrary to nephrotic rats, the ratio apo A-1/apo E mRNA was inverted in liver of pair-fed rats due to an increase in apo E mRNA. In conclusion, in nephrotic rats, the SSL of apo A-1 mRNA is i ncreased in liver and small intestine and appears to regulate the plas ma levels of apo A-1. These results also suggest a coordinated regulat ion of the apo A-1 and apo E gene expression in liver of nephrotic and pair-fed rats.