Proteome Research

Theme Leader :
Yuri Miura, Ph.D.
Researcher :
Hiroki Tsumoto, Ph.D., Keitarou Umezawa, Ph.D., Kyojiro Kawakami, Ph.D.

Proteome, Proteomics, Glycomics, Glycoproteomics, Post-translational modification, Healthy aging, Biomarker protein

1. 1.Proteome research on the post-translational modifications involved in age-related diseases.
2. 2.Proteome research on healthy aging.
3. 3.Proteome research on disease-related biomarker proteins.

"Proteome" is a compound of "protein" and "-ome", which means constitutive whole proteins including post-translational modifications. Proteomics is a strategy for analyzing proteome comprehensively. We perform proteomics based on two-dimensional gel electrophoresis and shotgun proteomics using isobaric tags for relative and absolute quantification (iTRAQ). We investigate proteins responsible for the mechanisms of aging and age-related diseases. O-linked β-N-acetylglucosamine (O-GlcNAc) is a reversible, post-translational, and regulatory modification of nuclear, mitochondrial, and cytoplasmic proteins. We examine the role of O-GlcNAc modification in the pathological mechanisms of diabetes, and search for biomarker proteins of diabetes-related complications. Furthermore, we performed glycoproteomic analysis of plasma proteins in Japanese semisuper centenarians (SSCs) (≥105 years). We expect that this approach will lead to the discovery of glycans and glycoproteins related to healthy aging.

1. 1. Nishihara, R., Kobayashi, K., Imae, R., Tsumoto, H., Manya, H., Mizuno, M., Kanagawa, M., Endo, T., Toda, T.: Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5, Biochem. Biophys.Res. Commun. 497, 1025-1030, (2018)
2. 2. Tsumoto, H., Akimoto, Y., Endo, T., Miura, Y.: Quantitative analysis of O-GlcNAcylation in combination with isobaric tag labeling and chemoenzymatic enrichment, Bioorg. Med. Chem. Lett. 27, 5022-5026, (2017)
3. 3. Kobayashi, M., Takeda, K., Narita, T., Nagai, K., Okita, N., Sudo, Y., Miura, Y., Tsumoto, H., Nakagawa, Y., Shimano, H., Higami, Y.: Mitochondrial intermediate peptidase is a novel regulator of sirtuin-3 activation by caloric restriction, FEBS Lett. 591, 4067-4073, (2017)
4. 4. Mellini, P., Itoh, Y., Tsumoto, H., Li, Y., Suzuki, M., Tokuda, N., Kakizawa, T., Miura, Y., Takeuchi, J., Lahtela-Kakkonen, M., Suzuki, T.: Potent mechanism-based sirtuin-2-selective inhibition by an in-situ-generated occupant of the substrate-binding site, “selectivity pocket” and NAD+-binding site, Chem. Sci., 8,　6400-6408,　(2017)
5. 5. Nishikaze, T., Tsumoto, H., Sekiya, S., Iwamoto, S., Miura, Y., Tanaka, K.: Differentiation of sialyl linkage isomers by one-pot sialic acid derivatization for mass spectrometry-based glycan profiling, Anal. Chem. 89, 2353-2360, (2017)
6. 6. Murakami, M., Kameda, K., Tsumoto, H., Tsuda, T., Masuda, K., Utsunomiya, R., Mori, H., Miura, Y., Sayama, K.: TLN-58, newly discovered hCAP18 processing form, found in the lesion vesicle of palmoplantar pustulosis in the skin, J. Invest. Dermatol.,137, 322-331, (2017)
7. 7. Akasaka-Manya, K., Kawamura, M., Tsumoto, H., Saitoh, Y., Kitazume, S., Hatsuda, H., Miura, Y., Hisanaga, S., Murayama, S., Hashimoto, Y., Manya, H., Endo, T.: Excess APP O-glycosylation by GalNAc-T6 decreases Aβ production, J. Biochemistry, 161, 99-111, (2017)
8. 8. Miura, Y., Endo, T.: Glycomics and glycoproteomics focused on aging and age-related diseases - Glycans as a potential biomarker for physiological alterations - Biochim. Biophys. Acta, -General Subjects- 1860, 1608-1614, (2016)
9. 9. Itoh Y, Aihara K, Mellini P, Tojo T, Ota Y, Tsumoto H, Solomon VR, Zhan P, Suzuki M, Ogasawara D, Shigenaga A, Inokuma T, Nakagawa H, Miyata N, Mizukami T, Otaka A, Suzuki T : Identification of SNAIL1 peptide-based irreversible lysine-specific demethylase 1-selective inactivators, J. Med. Chem. 59, 1531-1544, (2016)
10. 10. Miura, Y., Hashii, N., Tsumoto, H., Takakura, D., Ohta, Y., Abe, Y., Arai, Y., Kawasaki, N., Hirose, N., Endo, T., on behalf of SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians): Change in N-glycosylation of plasma proteins in Japanese semisupercentenarians, PLos One, 10, e0142645, (2015)
11. 11. Tsumoto, H., Ogasawara, D., Hashii, N., Suzuki, T., Akimoto, Y., Endo, T., Miura, Y.: Enrichment of O-GlcNAc-modified peptides using a novel thiol-alkyne and thiol-disulfide exchange, Bioorg. Med. Chem. Lett. 25, 2645-2649, (2015)
12. 12. Kawakami, K., Fujita, Y., Kato, T., Mizutani, K., Kameyama, K., Tsumoto, H., Miura, Y., Deguchi, T., Ito, M. : Integrin β4 and vinculin contained in exosomes are potential markers for progression of prostate cancer associated with taxane-resistance, Int. J. Oncol., 47, 384-390, (2015)
13. 13. Moriyama, T., Ito, A., Omote, S., Miura, Y., Tsumoto, H.: Heat-resistant characteristics of major royal jelly protein 1 (MRJP1) Oligomer, PLos One, 10, e0119169, (2015)
14. 14. Miura, Y., Iwamoto, M., Tsumoto, H., Endo, T., Toda, T.: Antioxidant effects of carnitine supplementation using fully automated two-dimensional chip gel electrophoresis, Electrophoresis Lett. 59, 109-111, (2015)
15. 15. Akimoto, Y., Miura, Y., Endo, T., Kawakami, H., Hart, G.W.: Diabetes and O-GlcNAcylation, In glycoscience：Biology and Medicine (Taniguchi, N., Endo, T., Hart, G.W., Seeberger, P.H., Wong, C-H., Eds.), Springer, 10.1007/SpringerReference_395455: 1207-1212, (2015)
16. 16. Kakizawa, T., Ota, Y., Itoh, Y., Tsumoto, H., Suzuki, T.: Histone H3 peptide based LSD1-selective inhibitors, Bioorg Med Chem Lett. 25,1925-8, (2015)
17. 17. Khan, M.N.A., Tsumoto, H., Itoh, Y., Ota, Y., Suzuki, M., Ogasawara, D., Nakagawa, H., Mizukami, T., Miyata N., Suzuki, T.: Design, synthesis, and biological activity of N-alkylated analogue of NCL1, a selective inhibitor of lysine-specific demethylase 1, Med. Chem. Commun., 6, 407-412, (2015)
18. 18. Iwamoto, M., Miura, Y., Tsumoto, H., Tanaka, Y., Morisawa, H., Endo, T., Toda, T.: Antioxidant effects of carnitine supplementation on 14-3-3 protein isoforms in the aged rat hippocampus detected using fully automated two-dimensional chip gel electrophoresis, Free Radic. Res., 48, 1409-16, (2014)
19. 19. Miura, Y., Sato, T., Sakurai, Y., Sakai, R., Hiraoka, W., Endo, T.: Hyper O-GlcNAcylation inhibits HSP 70-induction caused by sodium arsenite in HeLa cells, Biol. Pharm. Bull., 37, 1308-1314, (2014)
20. 20. Miura, Y., & Endo, T.: Challenge to successful aging -Proteomics on centenarians as a powerful tool for gerontology-, Biomedical Gerotology, 37, 23-27, (2013)
21. 21. Ogasawara, D., Itoh, Y., Tsumoto, H., Kakizawa, T., Mino, K., Fukuhara, K., Nakagawa, H., Hasegawa, M., Sasaki, R., Mizukami, T., Miyata, N., Suzuki, T.: Lysine-specific demethylase 1-selective unactivators: Protein-targeted drug delivery mechanism, Angew. Chem. Int. Ed., 52, 8620–8624, (2013)
22. 22. Ozawa, K., Komatsubara, A.T., Nishimura, Y., Sawada, T., Kawafune, H., Tsumoto, H., Tsuji, Y., Zhao, J., Kyotani, Y., Tanaka, T., Takahashi, R., Yoshizumi, M.: S-nitrosylation regulates mitochondrial quality control via activation of parkin, Sci. Rep., 3, 1-10, (2013)
23. 23. Miura, Y., Sakurai, Y., and Endo, T.: O-GlcNAc modification affects the ATM-mediated DNA damage response, Biochim. Biophys. Acta, -General Subjects- 1820, 1678-1685, (2012)
24. 24. Miura, Y., Sato, Y., Arai, Y., Abe, Y., Takayama, M., Toda, T., Hirose, N., and Endo, T.: Proteomic analysis of plasma proteins in Japanese semisuper centenarians. Exp. Gerontol. 46, 81-85, (2011)
25. 25. Akimoto, Y., Miura, Y., Toda, T., Wolfert, M. A., Wells, L., Boons, G. J., Hart,G. W., Endo, T., Kawakami, H. : Morphological changes in diabetic kidney are associated with increased O-GlcNAcylation of cytoskeletal proteins including α -Actinin 4, Clinical Proteomics, 8, 15, (2011)