Molecules and Cells

  • 제45권12호
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  • Pages.963-975
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  • 2022
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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SLC3A2 and SLC7A2 Mediate the Exogenous Putrescine-Induced Adipocyte Differentiation

  • Jin, Eom (Department of Biosciences, Mokpo National University) ;
  • Juhyun, Choi (Department of Biomedicine, Health & Life Convergence Sciences, BK21 Four, Biomedical and Healthcare Research Institute, Mokpo National University) ;
  • Sung-Suk, Suh (Department of Biosciences, Mokpo National University) ;
  • Jong Bae, Seo (Department of Biosciences, Mokpo National University)
  • 투고 : 2022.08.09
  • 심사 : 2022.12.21
  • 발행 : 2022.12.31
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초록

Exogenous polyamines are able to induce life span and improve glucose homeostasis and insulin sensitivity. However, the effects of exogenous polyamines on adipocyte differentiation and which polyamine transporters mediate them have not been elucidated yet. Here, we identified for the first time that exogenous polyamines can clearly stimulate adipocyte differentiation through polyamine transporters, solute carrier family 3 member A2 (SLC3A2) and SLC7A1. Exogenous polyamines markedly promote 3T3-L1 adipocyte differentiation by increasing the intracellular lipid accumulation and the expression of both adipogenic and lipogenic genes in a concentration-dependent manner. In particular, exogenous putrescine mainly regulates adipocyte differentiation in the early and intermediate stages. Moreover, we have assessed the expression of polyamine transporter genes in 3T3-L1 preadipocytes and adipocytes. Interestingly, the putrescine-induced adipocyte differentiation was found to be significantly suppressed in response to a treatment with a polyamine transporter inhibitor (AMXT-1501). Furthermore, knockdown experiments using siRNA that specifically targeted SLC3A2 or SLC7A2, revealed that both SLC3A2 and SLC7A2 act as important transporters in the cellular importing of exogenous putrescine. Thus, the exogenous putrescine entering the adipocytes via cellular transporters is involved in adipogenesis through a modulation of both the mitotic clonal expansion and the expression of master transcription factors. Taken together, these results suggest that exogenous polyamines (such as putrescine) entering the adipocytes through polyamine transporters, can stimulate adipogenesis.

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과제정보

This research was supported by a National Research Foundation of Korea (NRF) grant, funded by the Korean Government (MSIT; Nos. NRF-2019R1A2C1005719 and 2022R1A5A8033794).

참고문헌

  1. Abdulhussein, A.A. and Wallace, H.M. (2014). Polyamines and membrane transporters. Amino Acids 46, 655-660. https://doi.org/10.1007/s00726-013-1553-6
  2. Ali, A.T., Hochfeld, W.E., Myburgh, R., and Pepper, M.S. (2013). Adipocyte and adipogenesis. Eur. J. Cell Biol. 92, 229-236. https://doi.org/10.1016/j.ejcb.2013.06.001
  3. Bonhoure, N., Byrnes, A., Moir, R.D., Hodroj, W., Preitner, F., Praz, V., Marcelin, G., Chua, S.C., Jr., Martinez-Lopez, N., Singh, R., et al. (2015). Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes Dev. 29, 934-947. https://doi.org/10.1101/gad.258350.115
  4. Brenner, S., Bercovich, Z., Feiler, Y., Keshet, R., and Kahana, C. (2015). Dual regulatory role of polyamines in adipogenesis. J. Biol. Chem. 290, 27384-27392. https://doi.org/10.1074/jbc.M115.686980
  5. Bridges, R.J., Natale, N.R., and Patel, S.A. (2012). System xc-cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS. Br. J. Pharmacol. 165, 20-34. https://doi.org/10.1111/j.1476-5381.2011.01480.x
  6. Cani, P.D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A.M., Delzenne, N.M., and Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 57, 1470-1481. https://doi.org/10.2337/db07-1403
  7. Casero, R.A. and Pegg, A.E. (2009). Polyamine catabolism and disease. Biochem. J. 421, 323-338. https://doi.org/10.1042/BJ20090598
  8. Casero, R.A., Jr., Murray Stewart, T., and Pegg, A.E. (2018). Polyamine metabolism and cancer: treatments, challenges and opportunities. Nat. Rev. Cancer 18, 681-695. https://doi.org/10.1038/s41568-018-0050-3
  9. Casti, A., Orlandini, G., Reali, N., Bacciottini, F., Vanelli, M., and Bernasconi, S. (1982). Pattern of blood polyamines in healthy subjects from infancy to the adult age. J. Endocrinol. Invest. 5, 263-266. https://doi.org/10.1007/BF03348334
  10. Cerrada-Gimenez, M., Tusa, M., Casellas, A., Pirinen, E., Moya, M., Bosch, F., and Alhonen, L. (2012). Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism. Transgenic Res. 21, 843-853. https://doi.org/10.1007/s11248-011-9579-6
  11. Coburn, L.A., Singh, K., Asim, M., Barry, D.P., Allaman, M.M., Al-Greene, N.T., Hardbower, D.M., Polosukhina, D., Williams, C.S., Delgado, A.G., et al. (2019). Loss of solute carrier family 7 member 2 exacerbates inflammation-associated colon tumorigenesis. Oncogene 38, 1067-1079. https://doi.org/10.1038/s41388-018-0492-9
  12. Codoner-Franch, P., Tavarez-Alonso, S., Murria-Estal, R., Herrera-Martin, G., and Alonso-Iglesias, E. (2011). Polyamines are increased in obese children and are related to markers of oxidative/nitrosative stress and angiogenesis. J. Clin. Endocrinol. Metab. 96, 2821-2825. https://doi.org/10.1210/jc.2011-0531
  13. Darlington, G.J., Ross, S.E., and MacDougald, O.A. (1998). The role of C/EBP genes in adipocyte differentiation. J. Biol. Chem. 273, 30057-30060. https://doi.org/10.1074/jbc.273.46.30057
  14. Dobrovolskaite, A., Madan, M., Pandey, V., Altomare, D.A., an Phanstiel, O., 4th (2021). The discovery of indolone GW5074 during a comprehensive search for non-polyamine-based polyamine transport inhibitors. Int. J. Biochem. Cell Biol. 138, 106038.
  15. El Ouarrat, D., Isaac, R., Lee, Y.S., Oh, D.Y., Wollam, J., Lackey, D., Riopel, M., Bandyopadhyay, G., Seo, J.B., Sampath-Kumar, R., et al. (2020). TAZ is a negative regulator of PPARgamma activity in adipocytes and TAZ deletion improves insulin sensitivity and glucose tolerance. Cell Metab. 31, 162-173.e5. https://doi.org/10.1016/j.cmet.2019.10.003
  16. Hamouda, N.N., Van den Haute, C., Vanhoutte, R., Sannerud, R., Azfar, M., Mayer, R., Cortes Calabuig, A., Swinnen, J.V., Agostinis, P., Baekelandt, V., et al. (2021). ATP13A3 is a major component of the enigmatic mammalian polyamine transport system. J. Biol. Chem. 296, 100182.
  17. Igarashi, K. and Kashiwagi, K. (2010). Characteristics of cellular polyamine transport in prokaryotes and eukaryotes. Plant Physiol. Biochem. 48, 506-512. https://doi.org/10.1016/j.plaphy.2010.01.017
  18. Ishii, I., Ikeguchi, Y., Mano, H., Wada, M., Pegg, A.E., and Shirahata, A. (2012). Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells. Amino Acids 42, 619-626. https://doi.org/10.1007/s00726-011-1037-5
  19. Janne, J., Alhonen, L., Pietila, M., and Keinanen, T.A. (2004). Genetic approaches to the cellular functions of polyamines in mammals. Eur. J. Biochem. 271, 877-894. https://doi.org/10.1111/j.1432-1033.2004.04009.x
  20. Khan, A., Gamble, L.D., Upton, D.H., Ung, C., Yu, D.M.T., Ehteda, A., Pandher, R., Mayoh, C., Hebert, S., Jabado, N., et al. (2021). Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas. Nat. Commun. 12, 971.
  21. Kim, S., Lee, N., Park, E.S., Yun, H., Ha, T.U., Jeon, H., Yu, J., Choi, S., Shin, B., Yu, J., et al. (2021). T-cell death associated gene 51 is a novel negative regulator of PPARgamma that inhibits PPARgamma-RXRalpha heterodimer formation in adipogenesis. Mol. Cells 44, 1-12. https://doi.org/10.14348/molcells.2020.0143
  22. Kraus, D., Yang, Q., Kong, D., Banks, A.S., Zhang, L., Rodgers, J.T., Pirinen, E., Pulinilkunnil, T.C., Gong, F., Wang, Y.C., et al. (2014). Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature 508, 258-262. https://doi.org/10.1038/nature13198
  23. Landau, G., Ran, A., Bercovich, Z., Feldmesser, E., Horn-Saban, S., Korkotian, E., Jacob-Hirsh, J., Rechavi, G., Ron, D., and Kahana, C. (2012). Expression profiling and biochemical analysis suggest stress response as a potential mechanism inhibiting proliferation of polyamine-depleted cells. J. Biol. Chem. 287, 35825-35837. https://doi.org/10.1074/jbc.M112.381335
  24. Larsen, N., Vogensen, F.K., van den Berg, F.W., Nielsen, D.S., Andreasen, A.S., Pedersen, B.K., Al-Soud, W.A., Sorensen, S.J., Hansen, L.H., and Jakobsen, M. (2010). Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 5, e9085.
  25. Lefterova, M.I. and Lazar, M.A. (2009). New developments in adipogenesis. Trends Endocrinol. Metab. 20, 107-114. https://doi.org/10.1016/j.tem.2008.11.005
  26. Lewerenz, J., Hewett, S.J., Huang, Y., Lambros, M., Gout, P.W., Kalivas, P.W., Massie, A., Smolders, I., Methner, A., Pergande, M., et al. (2013). The cystine/glutamate antiporter system xc- in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid. Redox Signal. 18, 522-555. https://doi.org/10.1089/ars.2011.4391
  27. Ley, R.E., Backhed, F., Turnbaugh, P., Lozupone, C.A., Knight, R.D., and Gordon, J.I. (2005). Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U. S. A. 102, 11070-11075. https://doi.org/10.1073/pnas.0504978102
  28. Ley, R.E., Turnbaugh, P.J., Klein, S., and Gordon, J.I. (2006). Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022-1023. https://doi.org/10.1038/4441022a
  29. Li, J., Meng, Y., Wu, X., and Sun, Y. (2020). Polyamines and related signaling pathways in cancer. Cancer Cell Int. 20, 539.
  30. Linhart, H.G., Ishimura-Oka, K., DeMayo, F., Kibe, T., Repka, D., Poindexter, B., Bick, R.J., and Darlington, G.J. (2001). C/EBPalpha is required for differentiation of white, but not brown, adipose tissue. Proc. Natl. Acad. Sci. U. S. A. 98, 12532-12537. https://doi.org/10.1073/pnas.211416898
  31. Liu, M.R., Zhu, W.T., and Pei, D.S. (2021). System Xc- : a key regulatory target of ferroptosis in cancer. Invest. New Drugs 39, 1123-1131. https://doi.org/10.1007/s10637-021-01070-0
  32. Madan, M., Patel, A., Skruber, K., Geerts, D., Altomare, D.A., and Iv, O.P. (2016). ATP13A3 and caveolin-1 as potential biomarkers for difluoromethylornithine-based therapies in pancreatic cancers. Am. J. Cancer Res. 6, 1231-1252.
  33. McCubbrey, A.L., McManus, S.A., McClendon, J.D., Thomas, S.M., Chatwin, H.B., Reisz, J.A., D'Alessandro, A., Mould, K.J., Bratton, D.L., Henson, P.M., et al. (2022). Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells. Cell Rep. 38, 110222.
  34. Meireles, P., Mendes, A.M., Aroeira, R.I., Mounce, B.C., Vignuzzi, M., Staines, H.M., and Prudencio, M. (2017). Uptake and metabolism of arginine impact Plasmodium development in the liver. Sci. Rep. 7, 4072.
  35. Murray-Stewart, T.R., Woster, P.M., and Casero, R.A., Jr. (2016). Targeting polyamine metabolism for cancer therapy and prevention. Biochem. J. 473, 2937-2953. https://doi.org/10.1042/BCJ20160383
  36. Pegg, A.E. (2009). Mammalian polyamine metabolism and function. IUBMB Life 61, 880-894. https://doi.org/10.1002/iub.230
  37. Pegg, A.E. and Casero, R.A., Jr. (2011). Current status of the polyamine research field. Methods Mol. Biol. 720, 3-35. https://doi.org/10.1007/978-1-61779-034-8_1
  38. Pitocco, D., Di Leo, M., Tartaglione, L., De Leva, F., Petruzziello, C., Saviano, A., Pontecorvi, A., and Ojetti, V. (2020). The role of gut microbiota in mediating obesity and diabetes mellitus. Eur. Rev. Med. Pharmacol. Sci. 24, 1548-1562.
  39. Poulin, R., Casero, R.A., and Soulet, D. (2012). Recent advances in the molecular biology of metazoan polyamine transport. Amino Acids 42, 711-723. https://doi.org/10.1007/s00726-011-0987-y
  40. Ramos-Molina, B., Queipo-Ortuno, M.I., Lambertos, A., Tinahones, F.J., and Penafiel, R. (2019). Dietary and gut microbiota polyamines in obesity- and age-related diseases. Front. Nutr. 6, 24.
  41. Rosen, E.D., Walkey, C.J., Puigserver, P., and Spiegelman, B.M. (2000). Transcriptional regulation of adipogenesis. Genes Dev. 14, 1293-1307. https://doi.org/10.1101/gad.14.11.1293
  42. Roy, U.K., Rial, N.S., Kachel, K.L., and Gerner, E.W. (2008). Activated K-RAS increases polyamine uptake in human colon cancer cells through modulation of caveolar endocytosis. Mol. Carcinog. 47, 538-553. https://doi.org/10.1002/mc.20414
  43. Samal, K., Zhao, P., Kendzicky, A., Yco, L.P., McClung, H., Gerner, E., Burns, M., Bachmann, A.S., and Sholler, G. (2013). AMXT-1501, a novel polyamine transport inhibitor, synergizes with DFMO in inhibiting neuroblastoma cell proliferation by targeting both ornithine decarboxylase and polyamine transport. Int. J. Cancer 133, 1323-1333. https://doi.org/10.1002/ijc.28139
  44. Soda, K., Kano, Y., Sakuragi, M., Takao, K., Lefor, A., and Konishi, F. (2009). Long-term oral polyamine intake increases blood polyamine concentrations. J. Nutr. Sci. Vitaminol. (Tokyo) 55, 361-366. https://doi.org/10.3177/jnsv.55.361
  45. Song, J. and Deng, T. (2020). The adipocyte and adaptive immunity. Front. Immunol. 11, 593058.
  46. Soulet, D., Covassin, L., Kaouass, M., Charest-Gaudreault, R., Audette, M., and Poulin, R. (2002). Role of endocytosis in the internalization of spermidine-C2-BODIPY, a highly fluorescent probe of polyamine transport. Biochem. J. 367, 347-357. https://doi.org/10.1042/BJ20020764
  47. Soulet, D., Gagnon, B., Rivest, S., Audette, M., and Poulin, R. (2004). A fluorescent probe of polyamine transport accumulates into intracellular acidic vesicles via a two-step mechanism. J. Biol. Chem. 279, 49355-49366. https://doi.org/10.1074/jbc.M401287200
  48. Sugiyama, Y., Nara, M., Sakanaka, M., Gotoh, A., Kitakata, A., Okuda, S., and Kurihara, S. (2017). Comprehensive analysis of polyamine transport and biosynthesis in the dominant human gut bacteria: potential presence of novel polyamine metabolism and transport genes. Int. J. Biochem. Cell Biol. 93, 52-61. https://doi.org/10.1016/j.biocel.2017.10.015
  49. Tanaka, T., Yoshida, N., Kishimoto, T., and Akira, S. (1997). Defective adipocyte differentiation in mice lacking the C/EBPbeta and/or C/EBPdelta gene. EMBO J. 16, 7432-7443. https://doi.org/10.1093/emboj/16.24.7432
  50. Tang, Q.Q. and Lane, M.D. (1999). Activation and centromeric localization of CCAAT/enhancer-binding proteins during the mitotic clonal expansion of adipocyte differentiation. Genes Dev. 13, 2231-2241. https://doi.org/10.1101/gad.13.17.2231
  51. Tontonoz, P., Hu, E., and Spiegelman, B.M. (1994). Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 79, 1147-1156. https://doi.org/10.1016/0092-8674(94)90006-x
  52. van Veen, S., Martin, S., Van den Haute, C., Benoy, V., Lyons, J., Vanhoutte, R., Kahler, J.P., Decuypere, J.P., Gelders, G., Lambie, E., et al. (2020). ATP13A2 deficiency disrupts lysosomal polyamine export. Nature 578, 419-424. https://doi.org/10.1038/s41586-020-1968-7
  53. Wang, L., Chen, X., and Yan, C. (2022). Ferroptosis: an emerging therapeutic opportunity for cancer. Genes Dis. 9, 334-346. https://doi.org/10.1016/j.gendis.2020.09.005
  54. Yeon, J., Suh, S.S., Youn, U.J., Bazarragchaa, B., Enebish, G., and Seo, J.B. (2021). Methanol extract of Mongolian Iris bungei Maxim. stimulates 3T3- L1 adipocyte differentiation. J. Nanosci. Nanotechnol. 21, 3943-3949. https://doi.org/10.1166/jnn.2021.19160
  55. Zahedi, K., Barone, S., and Soleimani, M. (2022). Polyamines and their metabolism: from the maintenance of physiological homeostasis to the mediation of disease. Med. Sci. (Basel) 10, 38.