Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth

Jin Wu^{b, c},
Zongli Zhou^{b, c},
Yinghe Hu^{a, b, c},
Suzhen Dong^{a, b, c
, ,}

a.
Shanghai Engineering Research Center for Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062, China
b.
Institute of Chemical and Translational Genomics, East China Normal University, Shanghai 200062, China
c.
Shanghai Institute of Brain Functional Genomics, MOE & STCSM, Key Lab of Brain Functional Genomics, East China Normal University, Shanghai 200062, China

More Information

Corresponding author: E-mail address: dsz79@yahoo.com.cn (Suzhen Dong)

摘要

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Abstract: Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 (GPR41). In addition, it is an inhibitor of histone deacetylase (HDAC). Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the G1-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.
- GPR41 /
- Butyrate /
- HDAC inhibitor /
- Anti-proliferation /
- Cell cycle arrest

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参考文献(43)

[1]	Baradari, V., Huether, A., Hopfner, M. et al. Antiproliferative and proapoptotic effects of histone deacetylase inhibitors on gastrointestinal neuroendocrine tumor cells Endocr. Relat. Cancer, 13 (2006),pp. 1237-1250
[2]	Briscoe, C.P., Tadayyon, M., Andrews, J.L. et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids J. Biol. Chem., 278 (2003),pp. 11303-11311
[3]	Brown, A.J., Goldsworthy, S.M., Barnes, A.A. et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids J. Biol. Chem., 278 (2003),pp. 11312-11319
[4]	Cao, X.X., Mohuiddin, I., Ece, F. et al. Am. J. Respir. Cell Mol. Biol., 25 (2001),pp. 562-568
[5]	Chen, J.S., Faller, D.V., Spanjaard, R.A. Short-chain fatty acid inhibitors of histone deacetylases: promising anticancer therapeutics? Curr. Cancer Drug Targets, 3 (2003),pp. 219-236
[6]	Conley, B.A., Egorin, M.J., Tait, N. et al. Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors Clin. Cancer Res., 4 (1998),pp. 629-634
[7]	Covington, D.K., Briscoe, C.A., Brown, A.J. et al. The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing Biochem. Soc. Trans., 34 (2006),pp. 770-773
[8]	Davie, J.R. Inhibition of histone deacetylase activity by butyrate J. Nutr., 133 (2003),pp. 2485S-2493S
[9]	Dobbins, R.L., Chester, M.W., Daniels, M.B. et al. Circulating fatty acids are essential for efficient glucose-stimulated insulin secretion after prolonged fasting in humans Diabetes, 47 (1998),pp. 1613-1618
[10]	Duan, H., Heckman, C.A., Boxer, L.M. Histone deacetylase inhibitors down-regulate bcl-2 expression and induce apoptosis in t(14;18) lymphomas Mol. Cell. Biol., 25 (2005),pp. 1608-1619
[11]	Glozak, M.A., Seto, E. Histone deacetylases and cancer Oncogene, 26 (2007),pp. 5420-5432
[12]	Hinnebusch, B.F., Meng, S., Wu, J.T. et al. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation J. Nutr., 132 (2002),pp. 1012-1017
[13]	Itoh, Y., Kawamata, Y., Harada, M. et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40 Nature, 422 (2003),pp. 173-176
[14]	Johnstone, R.W. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer Nat. Rev. Drug Discov., 1 (2002),pp. 287-299
[15]	Kimura, I., Inoue, D., Maeda, T. et al. Proc. Natl. Acad. Sci. USA, 108 (2011),pp. 8030-8035
[16]	Kimura, M., Mizukami, Y., Miura, T. et al. J. Biol. Chem., 276 (2001),pp. 26453-26460
[17]	Kotarsky, K., Nilsson, N.E., Flodgren, E. et al. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs Biochem. Biophys. Res. Commun., 301 (2003),pp. 406-410
[18]	Kramer, O.H., Gottlicher, M., Heinzel, T. Histone deacetylase as a therapeutic target Trends Endocrinol. Metab., 12 (2001),pp. 294-300
[19]	Kuroiwa-Trzmielina, J., de Conti, A., Scolastici, C. et al. Chemoprevention of rat hepatocarcinogenesis with histone deacetylase inhibitors: efficacy of tributyrin, a butyric acid prodrug Int. J. Cancer, 124 (2009),pp. 2520-2527
[20]	Le Poul, E., Loison, C., Struyf, S. et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation J. Biol. Chem., 278 (2003),pp. 25481-25489
[21]	Li, R.W., Li, C. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells BMC Genomics, 7 (2006),p. 234
[22]	Marks, P., Rifkind, R.A., Richon, V.M. et al. Histone deacetylases and cancer: causes and therapies Nat. Rev. Cancer, 1 (2001),pp. 194-202
[23]	Milligan, G., Stoddart, L.A., Brown, A.J. G protein-coupled receptors for free fatty acids Cell Signal., 18 (2006),pp. 1360-1365
[24]	Mohana Kumar, B., Song, H.J., Cho, S.K. et al. Effect of histone acetylation modification with sodium butyrate, a histone deacetylase inhibitor, on cell cycle, apoptosis, ploidy and gene expression in porcine fetal fibroblasts J. Reprod. Dev., 53 (2007),pp. 903-913
[25]	Muhlethaler-Mottet, A., Meier, R., Flahaut, M. et al. Complex molecular mechanisms cooperate to mediate histone deacetylase inhibitors anti-tumour activity in neuroblastoma cells Mol. Cancer, 7 (2008),p. 55
[26]	Nielsen, S., Jorgensen, J.O., Hartmund, T. et al. Effects of lowering circulating free fatty acid levels on protein metabolism in adult growth hormone deficient patients Growth Horm. IGF Res., 12 (2002),pp. 425-433
[27]	Nolan, B., Duffy, A., Paquin, L. et al. Mitogen-activated protein kinases signal inhibition of apoptosis in lipopolysaccharide-stimulated neutrophils Surgery, 126 (1999),pp. 406-412
[28]	Ocker, M., Schneider-Stock, R. Int. J. Biochem. Cell Biol., 39 (2007),pp. 1367-1374
[29]	Peters, S.G., Pomare, E.W., Fisher, C.A. Portal and peripheral blood short chain fatty acid concentrations after caecal lactulose instillation at surgery Gut, 33 (1992),pp. 1249-1252
[30]	Rosato, R.R., Almenara, J.A., Dai, Y. et al. Simultaneous activation of the intrinsic and extrinsic pathways by histone deacetylase (HDAC) inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) synergistically induces mitochondrial damage and apoptosis in human leukemia cells Mol. Cancer Ther., 2 (2003),pp. 1273-1284
[31]	Samuel, B.S., Shaito, A., Motoike, T. et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41 Proc. Natl. Acad. Sci. USA, 105 (2008),pp. 16767-16772
[32]	Santini, V., Gozzini, A., Ferrari, G. Histone deacetylase inhibitors: molecular and biological activity as a premise to clinical application Curr. Drug Metab., 8 (2007),pp. 383-393
[33]	Siavoshian, S., Segain, J.P., Kornprobst, M. et al. Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression Gut, 46 (2000),pp. 507-514
[34]	Stoddart, L.A., Smith, N.J., Milligan, G. International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions Pharmacol. Rev., 60 (2008),pp. 405-417
[35]	Takai, N., Desmond, J.C., Kumagai, T. et al. Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells Clin. Cancer Res., 10 (2004),pp. 1141-1149
[36]	Tazoe, H., Otomo, Y., Kaji, I. et al. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions J. Physiol. Pharmacol., 59 (2008),pp. 251-262
[37]	Tazoe, H., Otomo, Y., Karaki, S. et al. Expression of short-chain fatty acid receptor GPR41 in the human colon Biomed. Res., 30 (2009),pp. 149-156
[38]	Topping, D.L., Clifton, P.M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides Physiol. Rev., 81 (2001),pp. 1031-1064
[39]	von Engelhardt, W., Bartels, J., Kirschberger, S. et al. Role of short-chain fatty acids in the hind gut Vet. Q, 20 (1998),pp. S52-S59
[40]	Xiong, Y., Miyamoto, N., Shibata, K. et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41 Proc. Natl. Acad. Sci. USA, 101 (2004),pp. 1045-1050
[41]	Xu, W.S., Parmigiani, R.B., Marks, P.A. Histone deacetylase inhibitors: molecular mechanisms of action Oncogene, 26 (2007),pp. 5541-5552
[42]	Yonezawa, T., Kobayashi, Y., Obara, Y. Cell Signal., 19 (2007),pp. 185-193
[43]	Yoo, C.B., Jones, P.A. Epigenetic therapy of cancer: past, present and future Nat. Rev. Drug Discov., 5 (2006),pp. 37-50