T. Shimokawa et al., HYPOCHOLESTEROLEMIC EFFECTS OF THE LDL RECEPTOR GENE TRANSCRIPTIONAL UPREGULATOR CP-230821, Journal of Biochemistry, 123(4), 1998, pp. 596-601
CP-230821 is a novel, potent LDL receptor gene transcriptional upregul
ator which decreases total plasma cholesterol level, Interestingly, th
is plasma LDL decrease does not alter hepatic lipid contents. A series
of experiments mas undertaken to study the molecular biology of this
phenomenon, Twelve hours after CP-230821 treatment, the transcriptiona
l activity and mRNA level of the LDL receptor gene in HepG2 cells were
increased by 264% and 426%, respectively, Although treatment with the
HMG-CoA reductase inhibitor compactin also increased LDL receptor gen
e transcription and mRNA, CP-230821 did not increase the level of HMG-
CoA reductase gene transcription or mRNA, These results indicate that
LDL receptor gene activity may play an important role in the decrease
of plasma LDL level. These results further suggest that the LDL recept
or gene and the HMG-CoA reductase gene are not strictly coordinately c
ontrolled.