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Cilostazol inhibits insulin-stimulated expression of sterol regulatory binding protein-1c via inhibition of LXR and Sp1

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Author(s)
Yun-A JungHee Kyoung KimKwi-Hyun BaeHye-Young SeoHye-Soon KimByoung Kuk JangGwon-Soo JungIn-Kyu LeeMi-Kyung KimKeun-Gyu Park
Keimyung Author(s)
Kim, Hye SoonJang, Byoung KukKim, Mi Kyung
Department
Dept. of Internal Medicine (내과학)
Journal Title
Experimental and Molecular Medicine.
Issued Date
2014
Volume
46
Issue
e73
Abstract
Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolic
syndrome. Sterol regulatory binding protein-1c (SREBP-1c) is a master regulator of lipogenic gene expression in the liver.
Hyperinsulinemia induces transcription of SREBP-1c via activation of liver X receptor (LXR) and specificity protein 1 (Sp1).
Cilostazol is an antiplatelet agent that prevents atherosclerosis and decreases serum triglyceride levels. However, little is known
about the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1c
transcription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin or
an LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. To
investigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays and
electrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-induced
expression of SREBP-1c and its downstream targets, acetyl-CoA carboxylase and fatty acid synthase, in cultured hepatocytes.
Cilostazol also inhibited activation of the SREBP-1c promoter by insulin, T0901317 and Sp1 in a luciferase reporter assay.
EMSA analysis showed that cilostazol inhibits SREBP-1c expression by repressing the binding of LXR and Sp1 to the promoter
region. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXR
and Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.
Experimental & Molecular Medicine (2014) 46, e73; doi:10.1038/emm.2013.143; published online 24 January 2014
Keywords: cilostazol; lipogenesis; LXR; Sp1; SREBP-1c
Keimyung Author(s)(Kor)
김혜순
장병국
김미경
Publisher
School of Medicine
Citation
Yun-A Jung et al. (2014). Cilostazol inhibits insulin-stimulated expression of
sterol regulatory binding protein-1c via inhibition
of LXR and Sp1. Experimental and Molecular Medicine., 46(e73), 1–8. doi: 10.1038/emm.2013.143
Type
Article
ISSN
1226-3613
DOI
10.1038/emm.2013.143
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35704
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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