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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2014.1
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- 1 - 8 (8page)
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Hepatic steatosis is common in obese individuals with hyperinsulinemia and is an important hepatic manifestation of metabolicsyndrome. 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 knownabout the effects of cilostazol on hepatic lipogenesis. Here, we examined the role of cilostazol in the regulation of SREBP-1ctranscription in the liver. The effects of cilostazol on the expression of SREBP-1c and its target genes in response to insulin oran LXR agonist (T0901317) were examined using real-time RT-PCR and western blot analysis on cultured hepatocytes. Toinvestigate the effect of cilostazol on SREBP-1c at the transcriptional level, transient transfection reporter assays andelectrophoretic mobility shift assays (EMSAs) were performed. Cilostazol inhibited insulin-induced and LXR-agonist-inducedexpression 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 promoterregion. These results indicate that cilostazol inhibits insulin-induced hepatic SREBP-1c expression via the inhibition of LXRand Sp1 activity and that cilostazol is a negative regulator of hepatic lipogenesis.
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참고문헌 (20)
참고문헌 신청
Azzout-Marniche D / 2000 / Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c)transcriptional activity in rat hepatocytes / Biochem J 350 (Pt 2) : 389
Becard D / 2001 / Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasi
Cagen LM / 2005 / Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c)promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis
Chen G / 2004 / Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver / Proc Natl Acad S
Deng X / 2007 / Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specifici
Becard D / 2001 / Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasi
Cagen LM / 2005 / Insulin activates the rat sterol-regulatory-element-binding protein 1c (SREBP-1c)promoter through the combinatorial actions of SREBP, LXR, Sp-1 and NF-Y cis
Chen G / 2004 / Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver / Proc Natl Acad S
Deng X / 2007 / Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specifici
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