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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 407 - 417 (11page)
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초록· 키워드
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We investigated the mechanism of spontaneous cholesterol
efflux induced by acyl-coenzyme A:cholesterol
acyltransferase (ACAT) inhibition, and how an alteration
of cholesterol metabolism in macrophages impacts
on that in HepG2 cells. Oleic acid anilide (OAA),
a known ACAT inhibitor reduced lipid storage substantially
by promotion of cholesterol catabolism and
repression of cholesteryl ester accumulation without
further increase of cytotoxicity in acetylated low-density
lipoprotein-loaded THP-1 macrophages. Analysis
of expressed mRNA and protein revealed that cholesterol
7α-hydroxylase (CYP7A1), oxysterol 7α- hydroxylase
(CYP7B1), and cholesterol 27-hydroxylase
(CYP27) were highly induced by ACAT inhibition. The
presence of a functional cytochrome P450 pathway
was confirmed by quantification of the biliary cholesterol
mass in cell monolayers and extracelluar
medium. Notably, massively secreted biliary cholesterol
from macrophages suppressed the expression of
CYP7 proteins in a farnesoid X receptor (FXR)-dependent manner in HepG2 cells. The findings reported here
provide new insight into mechanisms of spontaneous
cholesterol efflux, and suggest that ACAT inhibition
may stimulate cholesterol-catabolic (cytochrome P450)
pathway in lesion-macrophages, in contrast, suppress
it in hepatocyte via FXR induced by biliary cholesterol
(BC).
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참고문헌 (22)
참고문헌 신청
Avdeef A / 2005 / The rise of PAMPA / Expert Opin Drug Metab Toxicol 1 : 325 ~ 42
Axelson M / 1990 / Potential bile acid precursors in plasmapossible indicators of biosynthetic pathways to cholic and chenodeoxycholicacids in man / J Steroid Biochem 36 : 63
Basu SK / 1976 / Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts / Proc Nat
Batetta B / 2003 / Role of cholesterol ester pathway in the control of cell cycle in human aortic smooth muscle cells / FASEB J 17 : 746 ~ 8
Bligh EG / 1959 / A rapid method of total lipid extraction and purification / Can J Biochem Physiol 37 : 911 ~ 7
Axelson M / 1990 / Potential bile acid precursors in plasmapossible indicators of biosynthetic pathways to cholic and chenodeoxycholicacids in man / J Steroid Biochem 36 : 63
Basu SK / 1976 / Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts / Proc Nat
Batetta B / 2003 / Role of cholesterol ester pathway in the control of cell cycle in human aortic smooth muscle cells / FASEB J 17 : 746 ~ 8
Bligh EG / 1959 / A rapid method of total lipid extraction and purification / Can J Biochem Physiol 37 : 911 ~ 7
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