Abstract
Sterol regulatory element-binding protein-2 (SREBP-2) is a transcription factor regarded
as the main regulator of cholesterol homeostasis. Therefore, increased level of SREBP-2
could be responsible for hypercholesterolemia, which is observed in experimental chronic
renal failure (CRF). This study was designed primary to evaluate the impact of experimental
CRF (5/6 nephrectomy model) on rat liver SREBP-2 gene expression. In CRF rats, a twofold
increase in SREBP-2 mRNA level, as well as in mature SREBP-2 protein abundance was
found, when compared to control animals. It was associated with enhanced activity
and mRNA abundance of liver HMG-CoA reductase, a rate-limiting enzyme for cholesterol
biosynthesis. A twofold increase in liver cholesterologenesis rate was also noted.
We conclude that experimental CRF is associated with increased liver SREBP-2 gene
expression. This is probably the cause for enhanced HMG-CoA reductase gene expression
and, consequently, for increase in liver cholesterol synthesis in CRF rats. Despite
increased SREBP-2 gene expression we found LDL-receptor mRNA level to be lower than
in controls, suggesting SREBP-2 independent mechanisms of LDL-receptor transcriptional
regulation in CRF rats. Enhanced cholesterol synthesis and decreased LDL-receptor
mRNA level are probably responsible for an almost fourfold increase in serum cholesterol
concentration in CRF rats.
Keywords
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Article info
Publication history
Published online: June 30, 2006
Accepted:
May 23,
2006
Received in revised form:
May 12,
2006
Received:
December 4,
2005
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
