DOI QR코드

DOI QR Code

Proteomic Analysis in ob/ob Mice Before and After Hypoglycemic Polysaccharide Treatments

  • Published : 2009.10.31

Abstract

In an attempt to discover novel biomarker proteins in type 2 diabetes prognosis, we investigated the influence of hypoglycemic extracellular polysaccharides (EPS) obtained from the macrofungus Tremella fuciformis on the differential levels of plasma proteins in ob/ob mice using two-dimensional gel electrophoresis (2-DE). The 2-DE analysis demonstrated that 92 spots from about 900 visualized spots were differentially regulated, of which 40 spots were identified as principal diabetes-associated proteins. By comparing control with EPS-fed mice, we found that at least six proteins were significantly altered in ob/ob mice, including Apo A-I, IV, C-III, E, retinol-binding protein 4, and transferrin, and their levels were interestingly normalized after EPS treatment. Western blot analysis revealed that the altered levels of the two regulatory molecules highlighted in diabetes and obesity (e.g., resistin and adiponectin) were also normalized in response to EPS. The Mouse Diabetes PCR Array profiles showed that the expression of 84 genes related to the onset, development, and progression of diabetes were significantly downregulated in liver, adipocyte, and muscle of ob/ob mice. EPS might act as a potent regulator of gene expression for a wide variety of genes in ob/ob mice, particularly in obesity, insulin resistance, and complications from diabetes mellitus.

Keywords

References

  1. Bowers, R. R., J. W. Kim, T. C. Otto, and M. D. Lane. 2006. Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: Role of the BMP-4 gene. Proc. Natl. Acad. Sci. U.S.A. 103: 13022-13027 https://doi.org/10.1073/pnas.0605789103
  2. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  3. Cho, E. J., H. J. Hwang, S. W. Kim, J. Y. Oh, Y. M. Baek, J. W. Choi, and J. W. Yun. 2007. Hypoglycemic effects of exopolysaccharides produced by mycelial cultures of two different mushrooms Tremella fuciformis and Phellinus baumii in ob/ob mice. Appl. Microbiol. Biotechnol. 75: 1257-1265 https://doi.org/10.1007/s00253-007-0972-2
  4. Cho, E. J., J. Y. Oh, H. Y. Chang, and J. W. Yun. 2006. Production of exopolysaccharides by submerged mycelial culture of a mushroom Tremella fuciformis. J. Biotechnol. 127: 129-140 https://doi.org/10.1016/j.jbiotec.2006.06.013
  5. Curtiss, L. K. and W. A. Boisvert. 2000. Apolipoprotein E and atherosclerosis. Curr. Opin. Lipidol. 11: 243-251 https://doi.org/10.1097/00041433-200006000-00004
  6. Drew, B. G., N. H. Fidge, G. Gallon-Beaumier, B. E. Kemp, and B. A. Kingwell. 2004. High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 101:6999-7004 https://doi.org/10.1073/pnas.0306266101
  7. Ewart, R. B., S. Kornfeld, and D. M. Kipnis. 1975. Effect of lectins on hormone release from isolated rat islets of Langerhans. Diabetes 24: 705-714 https://doi.org/10.2337/diabetes.24.8.705
  8. Fathman, C. G., L. Soares, S. M. Chan, and P. J. Utz. 2005. An array of possibilities for the study of autoimmunity. Nature 435:605-611 https://doi.org/10.1038/nature03726
  9. Gao, X., S. Belmadani, A. Picchi, X. Xu, B. J. Potter, N. Tewari-Singh, S. Capobianco, W. M. Chilian, and C. Zhang. 2007. Tumor necrosis factor- $\alpha$induces endothelial dysfunction in $Lepr_{db}$ mice. Circulation 115: 245-254 https://doi.org/10.1161/CIRCULATIONAHA.106.650671
  10. Gavi, S., L. M. Stuart, P. Kelly, M. M. Melendez, D. C. Mynarcik, M. C. Gelato, and M. A. McNurlan. 2007. Retinolbinding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J. Clin. Endocrinol. Metab. 92: 1886-1890 https://doi.org/10.1210/jc.2006-1815
  11. Gochukwu, N. H., and N. E. Abady. 2003. Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats. Life Sci. 73: 1925-1938 https://doi.org/10.1016/S0024-3205(03)00543-5
  12. Golub, T. R., D. K. Slonim, P. Tamayo, C. Huard, M. Gaasenbeek, J. P. Mesirov, et al. 1999. Molecular classification of cancer: Class discovery and class prediction by gene expression monitoring. Science 286: 531-537 https://doi.org/10.1126/science.286.5439.531
  13. Gordon, D. J. and B. M. Rifkind. 1989. High-density lipoprotein - the clinical implications of recent studies. N. Engl. J. Med. 321: 1311-1316 https://doi.org/10.1056/NEJM198911093211907
  14. Graham, T. E., Q. Yang, M. Bl$\ddot{u}$her, A. Hammarstedt, T. P. Ciaraldi, R. R. Henry, et al. 2006. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N. Engl. J. Med. 354: 2552-2563 https://doi.org/10.1056/NEJMoa054862
  15. Gray, A. M. and P. R. Flatt. 1998. Insulin-releasing and insulinlike activity of Agaricus campestris (mushroom). J. Endocrinol. 157: 259-266 https://doi.org/10.1677/joe.0.1570259
  16. Gude, N., J. Muraski, M. Rubio, J. Kajstura, E. Schaefer, P. Anversa, and M. A. Sussman. 2006. Akt promotes increased cardiomyocyte cycling and expansion of the cardiac progenitor cell population. Circ. Res. 99: 381-388 https://doi.org/10.1161/01.RES.0000236754.21499.1c
  17. Hanniman, E. A., G. Lambert, Y. Inoue, F. J. Gonzalez, and C. J. Sinal. 2006. Apolipoprotein A-IV is regulated by nutritional and metabolic stress: Involvement of glucocorticoids, HNF-4 $\alpha$, and PGC-1 $\alpha$. J. Lipid Res. 47: 2503-2514 https://doi.org/10.1194/jlr.M600303-JLR200
  18. Hime, N. J., K. J. Drew, C. Hahn, P. J. Barter, and K. A. Rye. 2004. Apolipoprotein E enhances hepatic lipase-mediated hydrolysis of reconstituted high-density lipoprotein phospholipid and triacylglycerol in an isoform-dependent manner. Biochemistry 43: 12306-12314 https://doi.org/10.1021/bi036305i
  19. Hirosumi, J., G$\ddot{u}$rol Tuncman, L. Chang, C. Z. G$\ddot{o}$rg$\ddot{u}$n, K. T. Uysal, K. Maeda, M. Karin, and G$\ddot{o}$khan S. Hotamisligil. 2002. A central role for JNK in obesity and insulin resistance. Nature 420: 333-336 https://doi.org/10.1038/nature01137
  20. Hiukkam, A., J. Fruchart-Najib, E. Leinonen, H. Hilden, J. C. Fruchart, and M. R. Taskinen. 2005. Alterations of lipids and apolipoprotein CIII in very low density lipoprotein subspecies in type 2 diabetes. Diabetologia 48: 1207-1215 https://doi.org/10.1007/s00125-005-1753-z
  21. Hu, J. S., M. Durst, R. Kerb, V. Truong, J. T. Ma, E. Khurgin, D. Balaban, T. R. Gingeras, and B. B. Hoffman. 2000. Analysis of drug pharmacology towards predicting drug behavior by expression profiling using high-density oligonucleotide arrays. Ann. N. Y. Acad. Sci. 91: 9-15
  22. Igarashi, M., H. Wakasaki, N. Takahara, H. Ishii, Z. Y. Jiang, T. Yamauchi, et al. 1999. Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J. Clin. Invest. 103: 185-195 https://doi.org/10.1172/JCI3326
  23. Iida, S., Y. Sato, A. Nakaya, Y. Shinohara, Y. Hayashi, A. Sawada, et al. 2006. Genome wide expression analysis of white blood cells and liver of pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a cDNA microarray. Biol. Pharm. Bull. 29: 2451-2459 https://doi.org/10.1248/bpb.29.2451
  24. Jakupciak, J. P., G. D. Dakubo, S. Maragh, and R. L. Parr. 2006. Analysis of potential cancer biomarkers in mitochondrial DNA. Curr. Opin. Mol. Ther. 8: 500-506
  25. Kawashiri, M. A., C. Maugeais, and D. J. Rader. 2000. Highdensity lipoprotein metabolism: Molecular targets for new therapies for atherosclerosis. Curr. Atheroscler. Rep. 2: 363-372 https://doi.org/10.1007/s11883-000-0074-4
  26. Kiho, T., A. Yamane, J. Hui, S. Usui, and S. Ukai. 1996. Polysaccharides in fungi. XXXVI. Hypoglycemic activity of a polysaccharide (CS-F30) from the cultural mycelium of Cordyceps sinensis and its effect on glucose metabolism in mouse liver. Biol. Pharm. Bull. 19: 294-296 https://doi.org/10.1248/bpb.19.294
  27. Kiho, T., H. Morimoto, M. Sakushima, S. Usui, and S. Ukai. 1995. Polysaccharides in fungi. XXXV. Anti diabetic activity of an acidic polysaccharide from the fruiting bodies of Tremella aurantia. Biol. Pharm. Bull. 18: 1627-1629 https://doi.org/10.1248/bpb.18.1627
  28. Kiho, T., Y. Tsujimura, M. Sakushima, S. Usui, and S. Ukai. 1994. Polysaccharides in fungi. XXXIII. Hypoglycemic activity of an acidic polysaccharide (AC) from Tremella fuciformis. Yakugaku Zasshi 114: 308-315
  29. Kim, D. H., B. K. Yang, S. C. Jeong, J. B. Park, S. P. Cho, S. Das, J. W. Yun, and C. H. Song. 2001. Production of a hypoglycemic, extracellular polysaccharide from the submerged culture of the mushroom, Phellinus linteus. Biotechnol. Lett. 23:513-517 https://doi.org/10.1023/A:1010312513878
  30. Kim, D. H., B. K. Yang, S. C. Jeong, N. J. Hur, S. Das, J. W. Yun, J. W. Choi, Y. S. Lee, and C. H. Song. 2001. A preliminary study on the hypoglycemic effect of the exopolymers produced by five different medicinal mushrooms. J. Microbiol. Biotechnol. 11: 167-171
  31. Kim, S. W., H. J. Hwang, E. J. Cho, J. Y. Oh, Y. M. Baek, J. W. Choi, and J. W. Yun. 2006. Time-dependent plasma protein changes in streptozotocin-induced diabetic rats before and after fungal polysaccharide treatments. J. Proteome Res. 5: 2966-2976 https://doi.org/10.1021/pr0602601
  32. Kim, S. W., H. J. Hwang, H. M. Kim, M. C. Lee, M. S. Lee, J. W. Choi, and J. W. Yun. 2006. Effect of fungal polysaccharides on the modulation of plasma proteins in streptozotocin-induced diabetic rats. Proteomics 6: 5291-5302 https://doi.org/10.1002/pmic.200500933
  33. Korc, M. 2003. Diabetes mellitus in the era of proteomics. Mol. Cell Proteomics 2: 399-404
  34. Kotlyarov, A., A. Neininger, C. Schubert, R. Eckert, C. Birchmeier, H. D. Volk, and M. Gaestel. 1999. MAPKAP kinase 2 is essential for LPS-induced TNF-$\alpha$ biosynthesis. Nat. Cell Biol. 1: 94-97 https://doi.org/10.1038/10061
  35. Lee, J. H., J. W. Jr. Bullen, V. L. Stoyneva, and C. S. Mantzoros. 2005. Circulating resistin in lean, obese, and insulinresistant mouse models: Lack of association with insulinemia and glycemia. Am. J. Physiol. Endocrinol. Metab. 288: E625-E632 https://doi.org/10.1152/ajpendo.00184.2004
  36. Li, G., E. J. Barrett, M. O. Barrett, W. Cao, and Z. Liu. 2007. Tumor necrosis factor-alpha induces insulin resistance in endothelial cells via a p38 mitogen-activated protein kinasedependent pathway. Endocrinology 148: 3356-3363 https://doi.org/10.1210/en.2006-1441
  37. Mazzone, T. 1996. Apolipoprotein E secretion by macrophages:Its potential physiological functions. Curr. Opin. Lipidol. 7:303-307 https://doi.org/10.1097/00041433-199610000-00008
  38. McTernan, P. G., C. L. McTernan, R. Chetty, K. Jenner, F. M. Fisher, M. N. Lauer, J. Crocker, A. H. Barnett, and S. Kumar. 2002. Increased resistin gene and protein expression in human abdominal adipose tissue. J. Clin. Endocrinol. Metab. 87:2407-2410 https://doi.org/10.1210/jc.87.5.2407
  39. Murtaza, I., G. Marra, R. Schlapbach, A. Patrignani, M. Künzli, U. Wagner, J. Sabates, and A. Dutt. 2006. A preliminary investigation demonstrating the effect of quercetin on the expression of genes related to cell-cycle arrest, apoptosis and xenobiotic metabolism in human CO115 colon-adenocarcinoma cells using DNA microarray. Biotechnol. Appl. Biochem. 45:29-36 https://doi.org/10.1042/BA20060044
  40. Nadler, S. T., J. P. Stoehr, K. L. Schueler, G. Tanimoto, B. S. Yandell, and A. D. Attie. 2000. The expression of adipogenic genes is decreased in obesity and diabetes mellitus. Proc. Natl. Acad. Sci. U.S.A. 97: 11371-11376 https://doi.org/10.1073/pnas.97.21.11371
  41. Neumeier, M., A. Sigruener, E. Eggenhofer, J. Weigert, T. S. Weiss, A. Schaeffler, H. J. Schlitt, C. Aslanidis, and P. Piso. 2007. High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes. Biochem. Biophys. Res. Commun. 352: 543-548 https://doi.org/10.1016/j.bbrc.2006.11.058
  42. Norata, G. D., M. Ongari, K. Garlaschelli, S. Raselli, L. Grigore, and A. L. Catapano. 2007. Plasma resistin levels correlate with determinants of the metabolic syndrome. Eur. J. Endocrinol. 156: 279-284 https://doi.org/10.1530/eje.1.02338
  43. Olivero, O. A., A. M. Tejera, J. J. Fernandez, B. J. Taylor, S. Das, R. L. Divi, and M. C. Poirier. 2005. Zidovudine induces Sphase arrest and cell cycle gene expression changes in human cells. Mutagenesis 20: 139-146 https://doi.org/10.1093/mutage/gei019
  44. Ouchi, N., R. Shibata, and K. Walsh. 2006. Cardioprotection by adiponectin. Trends Cardiovasc. Med. 16: 141-146 https://doi.org/10.1016/j.tcm.2006.03.001
  45. Rangel-Moreno, J., L. Hartson, C. Navarro, M. Gaxiola, M. Selman, and T. D. Randall. 2006. Inducible bronchus-associated lymphoid tissue (iBALT) in patients with pulmonary complications of rheumatoid arthritis. J. Clin. Invest. 116: 3183-3194 https://doi.org/10.1172/JCI28756
  46. Ritorto, M. S. and J$\ddot{u}$rgen. Borlak. 2008. A simple and reliable protocol for mouse serum proteome profiling studies by use of two-dimensional electrophoresis and MALDI TOF/TOF mass spectrometry. Proteome Sci. 6: 25 https://doi.org/10.1186/1477-5956-6-25
  47. Rumberger, J. M., T. Jr. Peters, C. Burrington, and A. Green. 2004. Transferrin and iron contribute to the lipolytic effect of serum in isolated adipocytes. Diabetes 53: 2535-2541 https://doi.org/10.2337/diabetes.53.10.2535
  48. Sharma, A., S. Chavali, A. Mahajan, R. Tabassum, R. Banerjee, N. Tandon, and D. Bharadwaj. 2005. Genetic association, posttranslational modification, and protein-protein interactions in type 2 diabetes mellitus. Mol. Cell Proteomics 4: 1029-1037 https://doi.org/10.1074/mcp.M500024-MCP200
  49. Sherry, C. L., J. C. O’Connor, J. M. Kramer, and G. G. Freund. 2007. Augmented lipopolysaccharide-induced TNF-alpha production by peritoneal macrophages in type 2 diabetic mice is dependent on elevated glucose and requires p38 MAPK. J. Immunol. 178:663-670
  50. Shevchenko, A., M. Wilm, O. Vorm, and M. Mann. 1996. Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68: 850-858 https://doi.org/10.1021/ac950914h
  51. Solinas, G., W. Naugler, F. Galimi, M. S. Lee, and M. Karin. 2006. Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Proc. Natl. Acad. Sci. U.S.A. 103: 16454-16459 https://doi.org/10.1073/pnas.0607626103
  52. Sparre, T., R. Bergholdt, J$\phi$rn. Nerup, and F. Pociot. 2003. Application of genomics and proteomics in type 1 diabetes pathogenesis research. Expert Rev. Mol. Diagn. 3: 743-757 https://doi.org/10.1586/14737159.3.6.743
  53. Sreekumar, R., P. Halvatsiotis, J. C. Schimke, and K. S. Nair. 2002. Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment. Diabetes 51: 1913-1920 https://doi.org/10.2337/diabetes.51.6.1913
  54. Sundsten, T., M. Eberhardson, M. G$\ddot{o}$ransson, and P. Bergsten. 2006. The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes. Proteome Sci. 4: 22 https://doi.org/10.1186/1477-5956-4-22
  55. Tan, K. C., S. W. Shiu, Y. Wong, W. K. Wong, and S. Tam. 2006. Plasma apolipoprotein E concentration is an important determinant of phospholipid transfer protein activity in type 2 diabetes mellitus. Diabetes Metab. Res. Rev. 22: 307-312 https://doi.org/10.1002/dmrr.616
  56. Tokuyama, Y., H. Osawa, T. Ishizuka, H. Onuma, K. Matsui, T. Egashira, H. Makino, and A. Kanatsuka. 2007. Serum resistin level is associated with insulin sensitivity in Japanese patients with type 2 diabetes mellitus. Metabolism 56: 693-698 https://doi.org/10.1016/j.metabol.2006.12.019
  57. Vargas, L., M. E. Kawada, S. Bazaes, P. A. Karplus, and C. H. Faerman. 1998. Insulin antagonism: A novel role for human serum transferrin. Horm. Metab. Res. 30: 113-117 https://doi.org/10.1055/s-2007-978847
  58. Verg$\grave{e}$s, B., J. M. Petit, L. Duvillard, G. Dautin, E. Florentin, Fran$\c{c}$oise. Galland, and P. Gambert. 2006. Adiponectin is an important determinant of apoA-I catabolism. Arterioscler. Thromb. Vasc. Biol. 26: 1364-1369 https://doi.org/10.1161/01.ATV.0000219611.50066.bd
  59. Welsh, J. B., P. P. Zarrinkar, L. M. Sapinoso, S. G. Kern, C. A. Behling, B. J. Monk, D. J. Lockhart, R. A. Burger, and G. M. Hampton. 2001. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc. Natl. Acad. Sci. U.S.A. 98: 1176-1181 https://doi.org/10.1073/pnas.98.3.1176
  60. Wolf, G. 2007. Serum retinol-binding protein: A link between obesity, insulin resistance, and type 2 diabetes. Nutr. Rev. 65:251-256 https://doi.org/10.1111/j.1753-4887.2007.tb00302.x
  61. Yamauchi, T., J. Kamon, H. Waki, Y. Imai, N. Shimozawa, K. Hioki, et al. 2003. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J. Biol. Chem. 278: 2461-2468 https://doi.org/10.1074/jbc.M209033200
  62. Yang, Q., T. E. Graham, N. Mody, F. Preitner, O. D. Peroni, J. M. Zabolotny, K. Kotani, L. Quadro, and B. B. Kahn. 2005. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436: 356-362 https://doi.org/10.1038/nature03711
  63. Yue, L., N. Rasouli, G. Ranganathan, P. A. Kern, and T. Mazzone. 2004. Divergent effects of peroxisome proliferatoractivated receptor gamma agonists and tumor necrosis factor alpha on adipocyte ApoE expression. J. Biol. Chem. 279:47626-47632 https://doi.org/10.1074/jbc.M408461200
  64. Zhang, C. Y., Y. X. Feng, Y. Yu, W. J. Sun, J. Bai, F. Chen, and S. B. Fu. 2006. The molecular mechanism of resistance to methotrexate in mouse methotrexate-resistant cells by cancer drug resistance and metabolism SuperArray. Basic Clin. Pharmacol. Toxicol. 99: 141-145 https://doi.org/10.1111/j.1742-7843.2006.pto_470.x
  65. Zhang, H. N., and Z. B. Lin. 2004. Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacol. Sin. 25:191-195
  66. Zhan, Q., S. Signoretti, D. Whitaker-Menezes, T. M. Friedman, R. Korngold, and G. F. Murphy. 2007. Cytokeratin15-positive basal epithelial cells targeted in graft-versus-host disease express a constitutive antiapoptotic phenotype. J. Invest. Dermatol. 127:106-115 https://doi.org/10.1038/sj.jid.5700583
  67. Zisman, A., O. D. Peroni, E. D. Abel, M. D. Michael, F. Mauvais-Jarvis, B. B. Lowell, et al. 2000. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat. Med. 6: 924-928 https://doi.org/10.1038/78693

Cited by

  1. Neglected markers: Altered serum proteome in murine models of disease vol.12, pp.4, 2009, https://doi.org/10.1002/pmic.201100320
  2. Long-Term Regeneration and Functional Recovery of a 15 mm Critical Nerve Gap Bridged by Tremella fuciformis Polysaccharide-Immobilized Polylactide Conduits vol.2013, pp.None, 2009, https://doi.org/10.1155/2013/959261
  3. A proteomic approach to obesity and type 2 diabetes vol.19, pp.7, 2009, https://doi.org/10.1111/jcmm.12600
  4. Application of mass spectrometry based proteomics to understand diabetes: A special focus on interactomics vol.1868, pp.10, 2009, https://doi.org/10.1016/j.bbapap.2020.140469
  5. A review on the production, structure, bioactivities and applications of Tremella polysaccharides vol.35, pp.None, 2009, https://doi.org/10.1177/20587384211000541
  6. Moisture and caking resistant Tremella fuciformis polysaccharides microcapsules with hypoglycemic activity vol.146, pp.None, 2009, https://doi.org/10.1016/j.foodres.2021.110420