title: Regulation of apolipoprotein gene expression and plasma high-density lipoprotein composition in experimental nephrosis.
abstract: Hepatic and intestinal RNA levels were measured in rats made nephrotic by injection of puromycin aminonucleoside (PAN). The following increases in hepatic RNA levels, relative to controls, were measured: poly A+ (1.2), ribosomal (1.2), mRNA levels for transferrin (1.8), albumin (3.8) apolipoprotein (apo)E (2.3), apoB (2.5), apoA-II (1.9) and apoA-I (6.1). Increases of 1.5- to 2.2-fold in hepatic mRNA levels for albumin, apoA-II, apoB and apoE were measured in pre-nephrotic animals killed before the onset of proteinuria. Intestinal RNA levels in pre-nephrotic and nephrotic animals were not significantly different from control values. Transcription of the hepatic apoA-I gene increased 1.8-fold in nephrotic animals compared to controls. Immunological detection of apolipoproteins in high-density lipoproteins (HDL) separated by gradient gel electrophoresis indicated an increase in apoA-I and a decrease in apoA-IV and apoE containing HDL particles in nephrosis. To simulate the effects of increased apoA-I gene expression, human apoA-I was added to rat plasma in vivo and in vitro. ApoE was displaced from HDL by increased concentration of apoA-I. The results indicate that relatively small changes in apoA-I levels in the serum lead to significant changes in the apolipoprotein composition of HDL.
authors.affiliation: Russell Grimwade School of Biochemistry, University of Melbourne, Parkville, Australia.
authors.forename: J F
authors.initials: JF
authors.lastname: Marshall
authors.forename: J J
authors.initials: JJ
authors.lastname: Apostolopoulos
authors.forename: C M
authors.initials: CM
authors.lastname: Brack
authors.forename: G J
authors.initials: GJ
authors.lastname: Howlett
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A / Q000032:analysis / Q000494:pharmacology; D001057:Apolipoproteins E / Q000032:analysis; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D008099:Liver / Q000378:metabolism; D008297:Male; D009401:Nephrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D011692:Puromycin Aminonucleoside; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014158:Transcription, Genetic
chemical_list: D001053:Apolipoproteins; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; D011692:Puromycin Aminonucleoside