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

Experimental and Molecular Medicine

Volumn 46, Issue 1, 2014, Pages

  Jung, Yun A ^a   Kim, Hee Kyoung ^a   Bae, Kwi Hyun ^b   Seo, Hye Young ^a   Kim, Hye Soon ^a   Jang, Byoung Kuk ^a   Jung, Gwon Soo ^b   Lee, In Kyu ^b   Kim, Mi Kyung ^a   Park, Keun Gyu ^b  

^a Keimyung University School of Medicine   (South Korea)

^b Kyungpook National University School of Medicine   (South Korea)

Author keywords

Cilostazol; Lipogenesis; LXR; Sp1; SREBP 1c

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; CILOSTAZOL; FATTY ACID SYNTHASE; INSULIN; LIVER X RECEPTOR; N (2,2,2 TRIFLUOROETHYL) N [4 (2,2,2 TRIFLUORO 1 HYDROXY 1 TRIFLUOROMETHYLETHYL)PHENYL]BENZENESULFONAMIDE; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TRANSCRIPTION FACTOR SP1; FLUORINATED HYDROCARBON; ORPHAN NUCLEAR RECEPTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; SULFONAMIDE; TETRAZOLE DERIVATIVE; TO-901317;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOWNSTREAM PROCESSING; DRUG INHIBITION; ENZYME ACTIVATION; ENZYME REGULATION; GEL MOBILITY SHIFT ASSAY; HUMAN; HUMAN CELL; LIPOGENESIS; LIVER CELL; LUCIFERASE ASSAY; MOUSE; NONHUMAN; PROMOTER REGION; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; RECEPTOR BLOCKING; TRANSIENT TRANSFECTION; WESTERN BLOTTING; ANIMAL; C57BL MOUSE; CELL CULTURE; DRUG EFFECT; DRUG POTENTIATION; GENETICS; HEPG2 CELL LINE; METABOLISM; PROTEIN BINDING; RAT;

ANIMALS; CELLS, CULTURED; HEP G2 CELLS; HEPATOCYTES; HUMANS; HYDROCARBONS, FLUORINATED; INSULIN; LIPOGENESIS; MICE; MICE, INBRED C57BL; ORPHAN NUCLEAR RECEPTORS; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; RATS; SP1 TRANSCRIPTION FACTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; SULFONAMIDES; TETRAZOLES;

EID: 84896821256     PISSN: 12263613     EISSN: 20926413     Source Type: Journal    
DOI: 10.1038/emm.2013.143     Document Type: Article

References (24)

1. Targher G. Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of cardiovascular disease: the plot thickens. Diabet Med 2007; 24: 1-6.
2. Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84: 1513-1517.
3. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008; 118: 829-838.
4. Azzout-Marniche D, Becard D, Guichard C, Foretz M, Ferre P, Foufelle F. Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes. Biochem J 2000; 350 (Pt 2), 389-393.
5. Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G et al. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 1998; 101: 1-9.
6. Cagen LM, Deng X, Wilcox HG, Park EA, Raghow R, Elam MB. 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-acting elements. Biochem J 2005; 385: 207-216.
7. Chen G, Liang G, Ou J, Goldstein JL, Brown MS. 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 Sci USA 2004; 101: 11245-11250.
8. Schweizer M, Roder K, Zhang L, Wolf SS. Transcription factors acting on the promoter of the rat fatty acid synthase gene. Biochem Soc Trans 2002; 30: 1070-1072.
9. Shinoda-Tagawa T, Yamasaki Y, Yoshida S, Kajimoto Y, Tsujino T, Hakui N et al. A phosphodiesterase inhibitor, cilostazol, prevents the onset of silent brain infarction in Japanese subjects with type II diabetes. Diabetologia 2002; 45: 188-194.
10. Shinohara Y, Gotoh F, Tohgi H, Hirai S, Terashi A, Fukuuchi Y et al. Antiplatelet cilostazol is beneficial in diabetic and/or hypertensive ischemic stroke patients. Subgroup analysis of the cilostazol stroke prevention study. Cerebrovasc Dis 2008; 26: 63-70.
11. Katakami N, Kim YS, Kawamori R, Yamasaki Y. The phosphodiesterase inhibitor cilostazol induces regression of carotid atherosclerosis in subjects with type 2 diabetes mellitus: principal results of the Diabetic Atherosclerosis Prevention by Cilostazol (DAPC) study: a randomized trial. Circulation 2010; 121: 2584-2591.
12. Nakaya K, Ayaori M, Uto-Kondo H, Hisada T, Ogura M, Yakushiji E et al. Cilostazol enhances macrophage reverse cholesterol transport in vitro and in vivo. Atherosclerosis 2010; 213: 135-141.
13. Nakaya Y, Minami A, Sakamoto S, Niwa Y, Ohnaka M, Harada N et al. Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM. Diabetes Obes Metab 1999; 1: 37-41.
14. Fujita K, Nozaki Y, Wada K, Yoneda M, Endo H, Takahashi H et al. Effectiveness of antiplatelet drugs against experimental non-alcoholic fatty liver disease. Gut 2008; 57: 1583-1591.
15. Dif N, Euthine V, Gonnet E, Laville M, Vidal H, Lefai E. Insulin activates human sterol-regulatory-element-binding protein-1c (SREBP-1c) promoter through SRE motifs. Biochem J 2006; 400: 179-188.
16. Deng X, Yellaturu C, Cagen L, Wilcox HG, Park EA, Raghow R et al. Expression of the rat sterol regulatory element-binding protein-1c gene in response to insulin is mediated by increased transactivating capacity of specificity protein 1 (Sp1). J Biol Chem 2007; 282: 17517-17529.
17. Tani T, Uehara K, Sudo T, Marukawa K, Yasuda Y, Kimura Y. Cilostazol, a selective type III phosphodiesterase inhibitor, decreases triglyceride and increases HDL cholesterol levels by increasing lipoprotein lipase activity in rats. Atherosclerosis 2000; 152: 299-305.
18. Ginsberg HN, Zhang YL, Hernandez-Ono A. Regulation of plasma triglycerides in insulin resistance and diabetes. Arch Med Res 2005; 36: 232-240.
19. Becard D, Hainault I, Azzout-Marniche D, Bertry-Coussot L, Ferre P, Foufelle F. Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice. Diabetes 2001; 50: 2425-2430.
20. Liang G, Yang J, Horton JD, Hammer RE, Goldstein JL, Brown MS. Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory elementbinding protein-1c. J Biol Chem 2002; 277: 9520-9528.
21. Shimano H, Yahagi N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y et al. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem 1999; 274: 35832-35839.
22. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004; 114: 147-152.
23. Osborne TF. Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. J Biol Chem 2000; 275: 32379-32382.
24. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L et al. Role of LXRs in control of lipogenesis. Genes Dev 2000; 14: 2831-2838.