20(S)-protopanaxatriol inhibits liver X receptor alpha-mediatedexpression of lipogenic genes in hepatocytes

Collection with item attached
2015
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473414.do
DOI
10.1016/j.jphs.2015.05.007
Title
20(S)-protopanaxatriol inhibits liver X receptor alpha-mediatedexpression of lipogenic genes in hepatocytes
Description
This research was supported by a grant (A084335) of the Korea HealthTechnology R&D Project through the Korea Health Industry DevelopmentInstitute (KHIDI), funded by the Ministry of Health & Welfare, Republicof Korea; by a grant (NRF-2006-2005402) from the National ResearchFoundation of Korea Grants funded by the Korean Government; and byintramural grants (2010-352 and 2015-352) from the Asan Institute forLife Sciences, Seoul, Korea to SWK.
abstract
20(S)-protopanaxatriol (PPT) is an aglycone of ginsenosides isolated from Panax ginseng and has several interesting activities, including anti-inflammatory and anti-oxidative stress effects. Herein, PPT was identified as an inhibitor against the ligand-dependent transactivation of liver X receptor alpha (LXR alpha) using a Gal4-TK-luciferase reporter system. LXR alpha is a transcription factor of nuclear hormone receptor family and stimulates the transcription of many metabolic genes, such as lipogenesis-or reverse cholesterol transport (RCT)-related genes. Quantitative RT-PCR analysis showed that PPT inhibited the LXR alpha-dependent transcription of lipogenic genes, such as sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase, and stearoyl CoA desaturase 1. These inhibitory effects of PPT are, at least in part, a consequence of the reduced recruitment of RNA polymerase II to the LXR response element (LXRE) of the SREBP-1c promoter. Furthermore, LXR alpha-dependent triglyceride accumulation in primary mouse hepatocytes was significantly reduced by PPT. Interestingly, PPT did not inhibit the LXR alpha-dependent transcription of ABCA1, a crucial LXR alpha target gene involved in RCT. Chromatin immunoprecipitation assays revealed that PPT repressed recruitment of the lipogenic coactivator TRAP80 to the SREBP-1c LXRE, but not the ABCA1 LXRE. Overall, these data suggest that PPT has selective inhibitory activity against LXR alpha-mediated lipogenesis, but not LXR alpha-stimulated RCT. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
provenance
Made available in Cube on 2018-09-28T10:18:52Z (GMT). No. of bitstreams: 0
language
English
author
Oh, Gyun-Sik
Yoon, Jin
Lee, Gang Gu
Oh, Won Keun
Kim, Seung-Whan
accessioned
2018-09-28T10:18:52Z
available
2018-09-28T10:18:52Z
issued
2015
citation
JOURNAL OF PHARMACOLOGICAL SCIENCES(128): 2
issn
1347-8613
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473414.do
Funder
보건복지부
Funding Program
보건의료기술연구개발
Project ID
1465009960
Jurisdiction
Rep.of Korea
Project Name
Development of new drug target and treatment of metabolic syndrome
rights
openAccess
subject
20(S)-protopanaxatriol
Liver X receptor alpha
Sterol-regulatoryelement binding protein-1c
Lipogenesis
Steatosis
type
article


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