The small molecule phenamil is a modulator of adipocyte differentiation and PPARγ expression

Journal of Lipid Research

Volumn 51, Issue 9, 2010, Pages 2775-2784

  Park, Kye Won ^a,b,c   Waki, Hironori ^a,b   Choi, Sung Pil ^c   Park, Ki Moon ^c   Tontonoz, Peter ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Sungkyunkwan University   (South Korea)

Author keywords

Adipose tissue; Diabetes; ETS variant; Fatty acid; Nuclear receptor; Peroxisome proliferator activated receptor

Indexed keywords

2 [1 CARBOXY 2 [4 [2 (5 METHYL 2 PHENYL 4 OXAZOLYL)ETHOXY]PHENYL]ETHYLAMINO]BENZOIC ACID METHYL ESTER; DEXAMETHASONE; ISOBUTYLMETHYLXANTHINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PHENAMIL; SHORT HAIRPIN RNA; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ETV4; UNCLASSIFIED DRUG;

ADIPOCYTE; ADIPOGENESIS; ARTICLE; CELL ASSAY; CELL DIFFERENTIATION; CELL STRAIN 3T3; CELL STRUCTURE; CONTROLLED STUDY; DRUG DETERMINATION; DRUG SCREENING; DRUG STRUCTURE; GENE IDENTIFICATION; GENE OVEREXPRESSION; GENE TARGETING; PHARMACOLOGICAL BLOCKING; PRIORITY JOURNAL; PROADIPOCYTE; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION;

3T3 CELLS; ADIPOCYTES; AMILORIDE; ANIMALS; CCAAT-ENHANCER-BINDING PROTEIN-DELTA; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; GENE EXPRESSION REGULATION; HARMINE; MICE; MOLECULAR STRUCTURE; MONOAMINE OXIDASE INHIBITORS; OXAZOLES; PPAR GAMMA; PROTO-ONCOGENE PROTEINS C-ETS; SIGNAL TRANSDUCTION; SODIUM CHANNEL BLOCKERS; TRANSCRIPTION FACTORS; TYROSINE;

EID: 77956857406     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.M008490     Document Type: Article

References (33)

1. Tontonoz, P., E. Hu, and B. M. Spiegelman. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid- activated transcription factor. Cell. 79: 1147-1156.
2. Wu, Z., Y. Xie, N. L. Bucher, and S. R. Farmer. 1995. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev. 9: 2350-2363.
3. Oishi, Y., I. Manabe, K. Tobe, K. Tsushima, T. Shindo, K. Fujiu, G. Nishimura, K. Maemura, T. Yamauchi, N. Kubota, et al. 2005. Kruppel-like transcription factor KLF5 is a key regulator of adipocyte differentiation. Cell Metab. 1: 27-39.
4. Mori, T., H. Sakaue, H. Iguchi, H. Gomi, Y. Okada, Y. Takashima, K. Nakamura, T. Nakamura, T. Yamauchi, N. Kubota, et al. 2005. Role of Kruppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis. J. Biol. Chem. 280: 12867-12875.
5. Banerjee, S. S., M. W. Feinberg, M. Watanabe, S. Gray, R. L. Haspel, D. J. Denkinger, R. Kawahara, H. Hauner, and M. K. Jain. 2003. The Kruppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-gamma expression and adipogenesis. J. Biol. Chem. 278: 2581-2584.
6. Chen, Z., J. I. Torrens, A. Anand, B. M. Spiegelman, and J. M. Friedman. 2005. Krox20 stimulates adipogenesis via C/EBPbeta-dependent and -independent mechanisms. Cell Metab. 1: 93-106.
7. Tong, Q., G. Dalgin, H. Xu, C. N. Ting, J. M. Leiden, and G. S. Hotamisligil. 2000. Function of GATA transcription factors in preadipocyte-adipocyte transition. Science. 290: 134-138.
8. Kennell, J. A., E. E. O'Leary, B. M. Gummow, G. D. Hammer, and O. A. MacDougald. 2003. T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol. Cell. Biol. 23: 5366-5375.
9. Fajas, L., R. L. Landsberg, Y. Huss-Garcia, C. Sardet, J. A. Lees, and J. Auwerx. 2002. E2Fs regulate adipocyte differentiation. Dev. Cell. 3: 39-49.
10. Choy, L., and R. Derynck. 2003. Transforming growth factorbeta inhibits adipocyte differentiation by Smad3 interacting with CCAAT/enhancer-binding protein (C/EBP) and repressing C/EBP transactivation function. J. Biol. Chem. 278: 9609-9619.
11. Waki, H., K. W. Park, N. Mitro, L. Pei, R. Damoiseaux, D. C. Wilpitz, K. Reue, E. Saez, and P. Tontonoz. 2007. The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARgamma expression. Cell Metab. 5: 357-370.
12. Park, K. W., H. Waki, C. J. Villanueva, L. A. Monticelli, C. Hong, S. Kang, O. A. MacDougald, A. W. Goldrath, and P. Tontonoz. 2008. Inhibitor of DNA binding 2 is a small molecule-inducible modulator of peroxisome proliferator-activated receptor-gamma expression and adipocyte differentiation. Mol. Endocrinol. 22: 2038-2048.
13. Tontonoz, P., E. Hu, R. A. Graves, A. I. Budavari, and B. M. Spiegelman. 1994. mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev. 8: 1224-1234.
14. Forman, B. M., P. Tontonoz, J. Chen, R. P. Brun, B. M. Spiegelman, and R. M. Evans. 1995. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell. 83: 803-812.
15. Padilla, M. C., M. J. Armas-Hernandez, R. H. Hernandez, Z. H. Israili, and M. Valasco. 2007. Update of diuretics in the treatment of hypertension. Am. J. Ther. 14: 154-160.
16. Lant, A. F., A. J. Smith, and G. M. Wilson. 1969. Clinical evaluation of amiloride, a potassium-sparing diuretic. Clin. Pharmacol. Ther. 10: 50-63.
17. Benos, D. J. 1982. Amiloride: a molecular probe of sodium transport in tissues and cells. Am. J. Physiol. 242: C131-C145.
18. Frelin, C., P. Barbry, O. Chassande, P. Vigne, and M. Lazdunski. 1988. The structure of the amiloride sensitive apical Na+ channel from pig kidney. Kidney Int. 26 (Suppl.): S12-S13.
19. Kleyman, T. R., and E. J. Cragoe, Jr. 1988. Amiloride and its analogs as tools in the study of ion transport. J. Membr. Biol. 105: 1-21.
20. Blazer-Yost, B. L., and S. I. Helman. 1997. The amiloride-sensitive epithelial Na+ channel: binding sites and channel densities. Am. J. Physiol. 272: C761-C769.
21. Bobkov, Y. V., and B. W. Ache. 2007. Block by amiloride derivatives of odor-evoked discharge in lobster olfactory receptor neurons through action on a presumptive TRP channel. Chem. Senses. 32: 149-159.
22. Wu, Z., E. D. Rosen, R. Brun, S. Hauser, G. Adelmant, A. E. Troy, C. McKeon, G. J. Darlington, and B. M. Spiegelman. 1999. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol. Cell. 3: 151-158.
23. Park, K. W., H. Waki, W. K. Kim, B. S. Davies, S. G. Young, F. Parhami, and P. Tontonoz. 2009. The small molecule phenamil induces osteoblast differentiation and mineralization. Mol. Cell. Biol. 29: 3905-3914.
24. Kang, S., C. N. Bennett, I. Gerin, L. A. Rapp, K. D. Hankenson, and O. A. Macdougald. 2007. Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 282: 14515-14524.
25. Chassande, O., S. Renard, P. Barbry, and M. Lazdunski. 1994. The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter. J. Biol. Chem. 269: 14484-14489.
26. Shindoh, M., F. Higashino, and T. Kohgo. 2004. E1AF, an ets-oncogene family transcription factor. Cancer Lett. 216: 1-8.
27. de Launoit, Y., J. L. Baert, A. Chotteau-Lelievre, D. Monte, L. Coutte, S. Mauen, V. Firlej, C. Degerny, and K. Verreman. 2006. The Ets transcription factors of the PEA3 group: transcriptional regulators in metastasis. Biochim. Biophys. Acta. 1766: 79-87.
28. Funaoka, K., M. Shindoh, K. Yoshida, M. Hanzawa, K. Hida, S. Nishikata, Y. Totsuka, and K. Fujinaga. 1997. Activation of the p21(Waf1/Cip1) promoter by the ets oncogene family transcription factor E1AF. Biochem. Biophys. Res. Commun. 236: 79-82.
29. Inoue, N., N. Yahagi, T. Yamamoto, M. Ishikawa, K. Watanabe, T. Matsuzaka, Y. Nakagawa, Y. Takeuchi, K. Kobayashi, A. Takahashi, et al. 2008. Cyclin-dependent kinase inhibitor, p21WAF1/CIP1, is involved in adipocyte differentiation and hypertrophy, linking to obesity, and insulin resistance. J. Biol. Chem. 283: 21220-21229.
30. Lehmann, J. M., L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer. 1995. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J. Biol. Chem. 270: 12953-12956.
31. Lehrke, M., and M. A. Lazar. 2005. The many faces of PPARgamma. Cell. 123: 993-999.
32. Khoursheed, M., P. D. Miles, K. M. Gao, M. K. Lee, A. R. Moossa, and J. M. Olefsky. 1995. Metabolic effects of troglitazone on fat-induced insulin resistance in the rat. Metabolism. 44: 1489-1494.
33. Olefsky, J. M., and A. R. Saltiel. 2000. PPAR gamma and the treatment of insulin resistance. Trends Endocrinol. Metab. 11: 362-368.