K Irie

Summary

Affiliation: Kyoto University
Country: Japan

Publications

  1. pmc E22Δ Mutation in Amyloid β-Protein Promotes β-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity
    Takayuki Suzuki
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Int J Alzheimers Dis 2011:431320. 2010
  2. doi request reprint Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 606 8502, Japan
    Chem Rec 14:251-67. 2014
  3. doi request reprint Challenges to the development of bryostatin-type anticancer drugs based on the activation mechanism of protein kinase Cδ
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto, Japan
    Med Res Rev 32:518-35. 2012
  4. ncbi request reprint The toxic conformation of the 42-residue amyloid beta peptide and its relevance to oxidative stress in Alzheimer's disease
    K Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    Mini Rev Med Chem 7:1001-8. 2007
  5. ncbi request reprint Structure of beta-amyloid fibrils and its relevance to their neurotoxicity: implications for the pathogenesis of Alzheimer's disease
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    J Biosci Bioeng 99:437-47. 2005
  6. ncbi request reprint Toward the development of new medicinal leads with selectivity for protein kinase C isozymes
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Chem Rec 5:185-95. 2005
  7. ncbi request reprint Tumor promoter binding of the protein kinase C C1 homology domain peptides of RasGRPs, chimaerins, and Unc13s
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    Bioorg Med Chem 12:4575-83. 2004
  8. ncbi request reprint Indolactam and benzolactam compounds as new medicinal leads with binding selectivity for C1 domains of protein kinase C isozymes
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Curr Pharm Des 10:1371-85. 2004
  9. ncbi request reprint Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity
    Kazuhiro Irie
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, 606 8502, Kyoto, Japan
    Pharmacol Ther 93:271-81. 2002
  10. ncbi request reprint Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate
    K Irie
    Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan
    Biosci Biotechnol Biochem 64:2429-36. 2000

Collaborators

Detail Information

Publications39

  1. pmc E22Δ Mutation in Amyloid β-Protein Promotes β-Sheet Transformation, Radical Production, and Synaptotoxicity, But Not Neurotoxicity
    Takayuki Suzuki
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Int J Alzheimers Dis 2011:431320. 2010
    ..These data suggest that conformational change in E22Δ-Aβ is similar to that in E22P-Aβ42 but not the same, since E22Δ-Aβ42 exhibited no cytotoxicity, unlike E22P-Aβ42 and wild-type Aβ42...
  2. doi request reprint Synthesis and biological activities of simplified analogs of the natural PKC ligands, bryostatin-1 and aplysiatoxin
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 606 8502, Japan
    Chem Rec 14:251-67. 2014
    ..This review summarizes recent investigations on the simplification of natural PKC ligands, bryo-1 and ATX, to develop potential medicinal leads. ..
  3. doi request reprint Challenges to the development of bryostatin-type anticancer drugs based on the activation mechanism of protein kinase Cδ
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto, Japan
    Med Res Rev 32:518-35. 2012
    ..Moreover, its tumor-promoting activity in vitro was very weak, and its cell growth-inhibitory activities were comparable to those of bryo-1. These data suggest that aplog-1 could become another therapeutic lead for cancer...
  4. ncbi request reprint The toxic conformation of the 42-residue amyloid beta peptide and its relevance to oxidative stress in Alzheimer's disease
    K Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    Mini Rev Med Chem 7:1001-8. 2007
    ..Abeta42 is more neurotoxic than Abeta40. This review describes recent findings from a structural analysis of Abeta42 aggregates and discusses their relevance to neurotoxicity through the formation of radicals...
  5. ncbi request reprint Structure of beta-amyloid fibrils and its relevance to their neurotoxicity: implications for the pathogenesis of Alzheimer's disease
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    J Biosci Bioeng 99:437-47. 2005
    ..This review summarizes mainly our own recent findings from the structural analysis of A beta 42 fibrils and discusses its relevance to their neurotoxicity in vitro...
  6. ncbi request reprint Toward the development of new medicinal leads with selectivity for protein kinase C isozymes
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Chem Rec 5:185-95. 2005
    ..This invaluable information will lead to the structural optimization of the PKCdelta ligand as exemplified by the design and synthesis of naphtholactam-V8 (21)...
  7. ncbi request reprint Tumor promoter binding of the protein kinase C C1 homology domain peptides of RasGRPs, chimaerins, and Unc13s
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    Bioorg Med Chem 12:4575-83. 2004
    ..By the rapid screening system using this C1 peptide library, 5-prenyl-indolactam-V was identified as a promising lead for the novel protein kinase C isozyme specific ligands...
  8. ncbi request reprint Indolactam and benzolactam compounds as new medicinal leads with binding selectivity for C1 domains of protein kinase C isozymes
    Kazuhiro Irie
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Curr Pharm Des 10:1371-85. 2004
    ..Furthermore, our synthetic approach with the PKC C1 homology domains clarified that diacylglycerol kinase beta and gamma are new targets of phorbol esters...
  9. ncbi request reprint Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity
    Kazuhiro Irie
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, 606 8502, Kyoto, Japan
    Pharmacol Ther 93:271-81. 2002
    ..Moreover, we recently have found that a new lactone analogue of benzolactams (6) shows significant selectivity in PKCeta-C1B binding...
  10. ncbi request reprint Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate
    K Irie
    Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan
    Biosci Biotechnol Biochem 64:2429-36. 2000
    ..The results indicated that the beta-stereochemistry at position 12 of the phorbol skeleton is important for optimal activity. Binding selectivity to each PKC C1 domain of 1 was almost equal to that of PDBu...
  11. ncbi request reprint The amide hydrogen of (-)-indolactam-V and benzolactam-V8's plays a critical role in protein kinase C binding and tumor-promoting activities
    Y Nakagawa
    Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan
    Bioorg Med Chem Lett 11:723-8. 2001
    ..However, it is noteworthy that 6 showed significant selectivity in the PKC isozyme surrogate binding...
  12. ncbi request reprint The C4 hydroxyl group of phorbol esters is not necessary for protein kinase C binding
    M Tanaka
    Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan
    Bioorg Med Chem Lett 11:719-22. 2001
    ..These solution phase results differ from expectations based on the previously reported solid-phase structure of the complex of PKCdelta-C1B and phorbol-13-acetate (4b)...
  13. ncbi request reprint TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase
    K Shirakabe
    Department of Genetics and Molecular Biology, Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 01, Japan
    J Biol Chem 272:8141-4. 1997
    ..Furthermore, expression of a kinase-negative form of TAK1 interfered with the activation of SAPK/JNK induced by ceramide. These results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation...
  14. ncbi request reprint Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2
    T Moriguchi
    Department of Genetics and Molecular Biology, Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 01, Japan
    J Biol Chem 271:26981-8. 1996
    ..Thus, there are at least three members of p38 activator, MKK3, MKK3b, and MAPKK6, and MAPKK6 may function as a major activator for p38 when expressed...
  15. ncbi request reprint Synthesis, conformational analysis, and biological evaluation of 1-hexylindolactam-V10 as a selective activator for novel protein kinase C isozymes
    Ryo C Yanagita
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Med Chem 51:46-56. 2008
    ..Compound 5 selectively translocated novel PKC isozymes over conventional PKC isozymes in HeLa cells at 0.1-1 microM. These results suggest that 5 could be useful for the functional analysis of novel PKC isozymes...
  16. ncbi request reprint Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin
    K Irie
    Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan
    Int J Cancer 43:513-9. 1989
    ..This suggested that hydrophobicity rather than biological activity determines the cellular uptake of these fluorescent probes...
  17. ncbi request reprint Isomerization and/or racemization at Asp23 of Abeta42 do not increase its aggregative ability, neurotoxicity, and radical productivity in vitro
    Kazuma Murakami
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Biochem Biophys Res Commun 366:745-51. 2008
    ..These results suggest the isomerization and/or racemization of Asp23 not to be related to the pathogenesis, but to be a consequence of chemical reactions during the long-term deposition of fibrils...
  18. ncbi request reprint Synthesis and binding selectivity of 7- and 15-decylbenzolactone-V8 for the C1 domains of protein kinase C isozymes
    Yu Nakagawa
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Bioorg Med Chem Lett 13:3015-9. 2003
    ..These results indicate that the introduction of a hydrophobic substituent at position 8 of 4 is most effective in the development of PKC epsilon- and PKCeta-selective binders...
  19. ncbi request reprint Design and physicochemical properties of new fluorescent ligands of protein kinase C isozymes focused on CH/pi interaction
    Takuya Sugimoto
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Kyoto 606 8502, Japan
    Bioorg Med Chem 16:650-7. 2008
    ..These results suggest that 4 could be a useful probe for analyzing the interaction of tumor promoters with PKC C1 domains...
  20. pmc In vivo Neuroprotective Activity of Epopeptide AB Against Ischemic Damage
    Masaya Nagao
    Laboratory of Biosignals and Response, Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, 606 8502, Kyoto, Japan
    Cytotechnology 47:139-44. 2005
    ..Together with these results, Epopeptide AB did not transduce signals through direct binding to the known Epo receptor on hematopoietic cells but has neuroprotective activity against ischemia...
  21. ncbi request reprint Synthesis, aggregation, neurotoxicity, and secondary structure of various A beta 1-42 mutants of familial Alzheimer's disease at positions 21-23
    Kazuma Murakami
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Biochem Biophys Res Commun 294:5-10. 2002
    ..However, Flemish-type FAD needs alternative explanation except the aggregation and neurotoxicity of the corresponding A beta 1-42 mutant...
  22. ncbi request reprint Indolactam-V is involved in the CH/pi interaction with Pro-11 of the PKCdelta C1B domain: application for the structural optimization of the PKCdelta ligand
    Yu Nakagawa
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Am Chem Soc 127:5746-7. 2005
    ..The low binding affinity of BL-V8 could be enhanced by the effective formation of the CH/pi interaction as exemplified by the synthesis of naphtholactam-V8 (NL-V8)...
  23. ncbi request reprint Binding selectivity of conformationally restricted analogues of (-)-indolactam-V to the C1 domains of protein kinase C isozymes
    Akiko Masuda
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan
    Biosci Biotechnol Biochem 66:1615-7. 2002
    ..Although the binding constants of the cis amide-restricted analogue (2) were equal to those of 1, the trans amide-restricted analogue (3) bound significantly only to the novel PKC (delta, epsilon, eta, theta) isozymes...
  24. ncbi request reprint Neurotoxicity and physicochemical properties of Abeta mutant peptides from cerebral amyloid angiopathy: implication for the pathogenesis of cerebral amyloid angiopathy and Alzheimer's disease
    Kazuma Murakami
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Biol Chem 278:46179-87. 2003
    ..However, beta-turn is also a critical secondary structure because residues at positions 22 and 23 that preferably form two-residue beta-turn significantly enhanced the aggregative ability...
  25. ncbi request reprint Distance measurement between Tyr10 and Met35 in amyloid beta by site-directed spin-labeling ESR spectroscopy: implications for the stronger neurotoxicity of Abeta42 than Abeta40
    Kazuma Murakami
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Chembiochem 8:2308-14. 2007
    ..The difference in the distance between Abeta42 and Abeta40 could explain in part the stronger neurotoxicity of Abeta42 compared to Abeta40...
  26. doi request reprint Identification of physiological and toxic conformations in Abeta42 aggregates
    Yuichi Masuda
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Chembiochem 10:287-95. 2009
    ..The transition from the physiological conformation with a turn at positions 25 and 26 to the toxic conformation with a turn at positions 22 and 23 might be a key event in the pathogenesis of AD...
  27. ncbi request reprint Design and synthesis of 8-octyl-benzolactam-V9, a selective activator for protein kinase C epsilon and eta
    Yu Nakagawa
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Med Chem 49:2681-8. 2006
    ..These results indicate that 4 could be a selective activator for PKC epsilon and eta...
  28. ncbi request reprint A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3
    T Moriguchi
    Department of Genetics and Molecular Biology, Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto 606 01, Japan
    J Biol Chem 271:13675-9. 1996
    ..In addition, co-expression of TAK1 and p38/MPK2 in cells resulted in activation of p38/MPK2. These results indicate the existence of a novel kinase cascade consisting of TAK1, MAPKK6/MKK3, and p38/MPK2...
  29. ncbi request reprint Analysis of the secondary structure of beta-amyloid (Abeta42) fibrils by systematic proline replacement
    Akira Morimoto
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Biol Chem 279:52781-8. 2004
    ..The identification of the beta-sheet region of Abeta42 is a basis for designing new aggregation inhibitors of Abeta peptides...
  30. ncbi request reprint Formation and stabilization model of the 42-mer Abeta radical: implications for the long-lasting oxidative stress in Alzheimer's disease
    Kazuma Murakami
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Am Chem Soc 127:15168-74. 2005
    ..In contrast, the S-oxidized radical cation of Abeta40 is too short-lived to induce potent neurotoxicity because no such stabilization of radicals occurs in Abeta40...
  31. doi request reprint Verification of the C-terminal intramolecular beta-sheet in Abeta42 aggregates using solid-state NMR: implications for potent neurotoxicity through the formation of radicals
    Yuichi Masuda
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    Bioorg Med Chem Lett 18:3206-10. 2008
    ..The S-oxidized radical cation at Met-35, an ultimate radical species responsible for neurotoxicity, could be stabilized by the carboxylate anion at the C-terminus, resulting in aggregation to cause long-term oxidative stress...
  32. ncbi request reprint Verification of the intermolecular parallel beta-sheet in E22K-Abeta42 aggregates by solid-state NMR using rotational resonance: implications for the supramolecular arrangement of the toxic conformer of Abeta42
    Yuichi Masuda
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan
    Biosci Biotechnol Biochem 72:2170-5. 2008
    ..The results also suggest that each conformer would not accumulate alternately, but form a relatively large assembly...
  33. ncbi request reprint Verification of the turn at positions 22 and 23 of the beta-amyloid fibrils with Italian mutation using solid-state NMR
    Yuichi Masuda
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Bioorg Med Chem 13:6803-9. 2005
    ..The formation of a salt bridge between Lys-22 and Asp-23 in the minor conformer might be a reason why E22K-Abeta42 is more pathogenic than wild-type Abeta42...
  34. ncbi request reprint Aggregation and neurotoxicity of mutant amyloid beta (A beta) peptides with proline replacement: importance of turn formation at positions 22 and 23
    Akira Morimoto
    Laboratory of Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Sakyo ku, Kyoto 606 8502, Japan
    Biochem Biophys Res Commun 295:306-11. 2002
    ..Since proline has a propensity for beta-turn structure as a Pro-X corner, these data implicate that beta-turn formation at positions 22 and 23 plays a crucial role in the aggregation and neurotoxicity of A beta peptides...
  35. doi request reprint A simple analogue of tumor-promoting aplysiatoxin is an antineoplastic agent rather than a tumor promoter: development of a synthetically accessible protein kinase C activator with bryostatin-like activity
    Yu Nakagawa
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606 8502, Japan
    J Am Chem Soc 131:7573-9. 2009
    ..This study provides a synthetically accessible PKC activator with bryo-1-like activities, which could be another therapeutic lead for cancer, AD, and AIDS...
  36. ncbi request reprint In vitro covalent binding proteins of zerumbone, a chemopreventive food factor
    Kohta Ohnishi
    Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan
    Biosci Biotechnol Biochem 73:1905-7. 2009
    ..7 macrophages. Using the ZER-bound Sepharose gel, it appeared ZER was covalently bound to proteins, Keap1 and HuR, that play key roles in these molecular mechanisms...
  37. pmc Downregulation of programmed cell death 4 by inflammatory conditions contributes to the generation of the tumor promoting microenvironment
    Michiko Yasuda
    Kyoto University, Japan
    Mol Carcinog 49:837-48. 2010
    ..Taken together, loss of Pdcd4 in macrophages may be a critical step in establishing the inflammatory environment while that in tumor cells contributes to tumor progression...
  38. ncbi request reprint Synthesis and phorbol ester binding of the cysteine-rich domains of diacylglycerol kinase (DGK) isozymes. DGKgamma and DGKbeta are new targets of tumor-promoting phorbol esters
    Mayumi Shindo
    Applied Biosystems Japan Ltd, 4 5 4 Hacchobori, Chuo Ku, Tokyo 104 0032, Japan
    J Biol Chem 278:18448-54. 2003
    ..These results indicate that 12-O-tetradecanoylphorbol 13-acetate binds to C1A of DGKgamma to cause its translocation...
  39. ncbi request reprint Analysis of the non-covalent interaction between metal ions and the cysteine-rich domain of protein kinase C eta by electrospray ionization mass spectrometry
    Mayumi Shindo
    Applied Biosystems Japan Ltd, 4 5 4Hacchobori, Chuo Ku, Tokyo, 104 0032, Japan
    Bioorg Med Chem 11:5075-82. 2003
    ..These data suggest that the copper treatment formed three intramolecular S-S bonds to abolish the PDBu binding of PKCeta-C1B...