Down-regulation of hepatic high-density lipoprotein receptor, SR-B1, in nephrotic syndrome.
BACKGROUND
Nephrotic syndrome (NS) is a prototype of acquired hypercholesterolemia. Hepatic synthesis and removal of cholesterol play major roles in the regulation of plasma concentration of this sterol. Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles are the primary vehicles for cholesterol transport to the liver. We have recently demonstrated that NS results in acquired hepatic LDL receptor deficiency in rats. This study was undertaken to determine the effect of NS on hepatic expression of the newly discovered, long-sought HDL receptor.


METHODS
Hepatic HDL receptor and apolipoprotein A-I (apo A-I) expressions were studied in rats with puromycin-induced NS. The results were compared with those obtained in placebo-treated, normal controls.


RESULTS
The NS group exhibited a marked reduction in hepatic tissue HDL receptor protein abundance when compared with the control group. In contrast, hepatic HDL receptor mRNA abundance in the NS group was similar to that of the control group. As expected, the NS group showed a marked increase in hepatic apo A-I mRNA abundance.


CONCLUSIONS
The study explored the effect of experimental NS on hepatic HDL receptor expression, and the results revealed a marked down-regulation of HDL receptor in rats with NS. In contrast, hepatic expression of Apo A-I, the principal protein constituent of HDL, was markedly increased in NS rats. The HDL receptor deficiency shown here can potentially limit the efficiency of HDL as the primary vehicle for reverse cholesterol transport in NS.
Liang
K
K
Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, USA.
Vaziri
N D
ND
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D015153:Blotting, Western; D002352:Carrier Proteins; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL; D008297:Male; D008565:Membrane Proteins; D009404:Nephrotic Syndrome / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011507:Proteinuria / Q000235:genetics / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D017931:DNA Primers; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D011691:Puromycin