Induction of ABCA1 by overexpression of hormone-sensitive lipase in macrophages
Initial step toward the reverse-cholesterol transport is cholesterol efflux that is mediated by the ATP-binding cassette transporter A1 (ABCA1). However, it is unknown how the cholesteryl ester (CE) hydrolysis induces the expression of the ABCA1 gene. Overexpression of hormone-sensitive lipase (HSL)...
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Published in | Biochemical and biophysical research communications Vol. 376; no. 1; pp. 111 - 115 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
07.11.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Initial step toward the reverse-cholesterol transport is cholesterol efflux that is mediated by the ATP-binding cassette transporter A1 (ABCA1). However, it is unknown how the cholesteryl ester (CE) hydrolysis induces the expression of the ABCA1 gene. Overexpression of hormone-sensitive lipase (HSL) increased the hydrolysis of CE and stimulated the expression of ABCA1 gene at the transcriptional level in RAW 264.7 macrophages. The stimulatory effects of the HSL overexpression and cholesterol loading on the ABCA1 promoter activity were additive. Mutational analyses of the promoter of ABCA1 identified the responsible element as the direct repeat-4 (DR-4) that binds LXR/RXR heterodimers. In conclusion, stimulation of hydrolysis of CE in macrophages induces the expression of ABCA1 gene primarily via the LXR-dependent pathway and can be useful for the prevention of atherosclerosis. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0006-291X 1090-2104 |
DOI: | 10.1016/j.bbrc.2008.08.101 |