Elucidation of a new differentiation mechanism of beige adipocytes and its application for drug design

• Project/Area Number: 26670124
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Kobe University
• Principal Investigator: SAITO NAOAKI 神戸大学, バイオシグナル研究センター, 教授 (60178499)
• Co-Investigator(Kenkyū-buntansha): UEYAMA Takehiko 神戸大学, バイオシグナル研究センター, 准教授 (80346254)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 脂肪細胞 / 分化誘導因子 / ケラチノサイト / Rac

Outline of Final Research Achievements

We studied a new Rac-medicated pathway which can induce　the differentiation of adipocytes. Using DNA microarray and RT-PCR, we found 5 factors (a,b,c,d,e) secreted from keraninocytes when Rac-mediated pathway is activated. Differentiation of adipocyte (3T3-L1 cells) was significantly enhanced when the cells were treated with the combination of a+b or a+c, much more than treated with a, b or c alone. We further elucidate whether the signal induces the diffentiation to white or beige adipocyte and we study the new drug target for the disorder of lipid/glucose metabolim.

Research Products

• [Journal Article] Essential role of constitutive androstane receptor in Ginkgo biloba extract induced liver hypertrophy and hepatocarcinogenesis (2015)
  • Author(s): Maeda J, Inoue K, Ichimura R, Takahashi M, Kodama Y, Saito N, Yoshida M.
  • Journal Title: Food Chem Toxicol. Volume: 83 Pages: 201-209
  • DOI: 10.1016/j.fct.2015.06.010
  • Peer Reviewed / Open Access
• [Journal Article] The Extracellular A-loop of Dual Oxidases Affects the Specificity of Reactive Oxygen Species Release. (2015)
  • Author(s): Ueyama T, Sakuma M, Ninoyu Y, Hamada T, Dupuy C, Geiszt M, Leto TL, Saito N.
  • Journal Title: J Biol. Chem Volume: 290 Issue: 10 Pages: 6495-6506
  • DOI: 10.1074/jbc.m114.592717
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification and characterization of PKCγ, a kinase associated with SCA14, as an amyloidogenic protein. (2015)
  • Author(s): Takahashi H, Adachi N, Shirafuji T, Danno S, Ueyama T, Vendruscolo M, Shuvaev AN, Sugimoto T, Seki T, Hamada D, Irie K, Hirai H, Sakai N, *Saito N.
  • Journal Title: Hum Mol Genet. Volume: 24 Issue: 2 Pages: 525-539
  • DOI: 10.1093/hmg/ddu472
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The role of Pak-interacting exchange factor-β phosphorylation at serines 340 and 583 by PKCγ in dopamine release. (2014)
  • Author(s): Shirafuji T, Ueyama T, Yoshino K, Takahashi H, Adachi N, Ago Y, Koda K, Nashida T, Hiramatsu N, Matsuda T, Toda T, Sakai N, Saito N.
  • Journal Title: J Neurosci Volume: 34 Issue: 28 Pages: 9268-9280
  • DOI: 10.1523/jneurosci.4278-13.2014
  • NAID: 120005619641
  • Peer Reviewed / Open Access
• [Journal Article] Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells (2014)
  • Author(s): Ueyama T, Sakaguchi H, Nakamura T, Goto A, Morioka S, Shimizu A, Nakao K, Hishikawa Y, Ninoyu Y, Kassai H, Suetsugu S, Koji T, Fritzsch B, Yonemura S, Hisa Y, Matsuda M, Aiba A, Saito N.
  • Journal Title: J Cell Sci. Volume: 127 Pages: 2040-2052
  • DOI: 10.1242/jcs.143602
  • NAID: 120006986582
  • Peer Reviewed / Open Access
• [Journal Article] Heparin inhibits melanosome uptake and inflammatory response coupled with phagocytosis through blocking PI3k/Akt and MEK/ERK signaling pathways in human epidermal keratinocytes. (2014)
  • Author(s): Makino-Okamura C, Niki Y, Takeuchi S, Nishigori C, Declercq L, Yaroch DB, Saito N.
  • Journal Title: Pigment Cell Melanoma Res. Volume: 27 Issue: 6 Pages: 1063-1074
  • DOI: 10.1111/pcmr.12287
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCa signaling pathway (2014)
  • Author(s): Maillard, L., Saito, N., Hlawaty, H., Friand, V., Suffee, N., Chmilewsky, F., Haddad, O., Laguillier, C., Guyot, E., Ueyama, T., Oudar, O., Sutton, A., Charnaux, N.
  • Journal Title: Biology Open Volume: 3 Issue: 10 Pages: 995-1004
  • DOI: 10.1242/bio.20148227
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Both the C1 domain and a basic amino acid cluster at C-terminus are important for neurite and branch induction ability of DGK. (2014)
  • Author(s): Takuya Kano, Takeshi Kouzuki, Satoru Mizuno, Shuji Ueda, Minoru Yamanoue, Fumio Sakane, Naoaki Saito and Yasuhito Shirai
  • Journal Title: iochem. Biophys. Res. Commun Volume: 印刷中 Issue: 1 Pages: 89-94
  • DOI: 10.1016/j.bbrc.2014.03.113
  • Peer Reviewed / Open Access
• [Journal Article] Diacylglycerol kinase gamma regulates antigen-induced mast cell degranulation by mediating Ca2+ influxes (2014)
  • Author(s): Sakuma, M., Shirai, Y., Ueyama, T., and Saito, N.
  • Journal Title: Biochem. Biophys. Res. Commun, Volume: 445 Issue: 2 Pages: 340-345
  • DOI: 10.1016/j.bbrc.2014.01.197
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Protein kinase C and its involvement in neuronal diseases (2016)
  • Author(s): Naoaki Saito
  • Organizer: Neuroscience Network in Kobe シンポジウム
  • Place of Presentation: 神戸大学（兵庫県・神戸市）
  • Year and Date: 2016-02-19
  • Invited
• [Presentation] 脊髄小脳変性症14型におけるPKCのアミロイド様構造体の形成と疾患への関与 (2015)
  • Author(s): 足立直子、高橋英之、白藤俊彦、上山健彦、Michele, Vendruscolo., 入江一浩、平井宏和、酒井規雄、齋藤尚亮
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2015-07-28
• [Presentation] ・Maintenance of stereocillia and apical junctional complexes by Cdc42 in cochlear hair cells. (2014)
  • Author(s): Ueyama, T., Sakaguchi,H., Nakamura, T., Goto, A., Morioka, S., Fritzsch, B., Hisa, Y., Matsuda, M., Aiba, A. and Saito, N.
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Cdc42 is required for maintenance of stereocilia and apical junctional complexes in cochlear hair cells. (2014)
  • Author(s): Ueyama, T., Sakaguchi, H., Goto, A., Hisa, Y., Matsuda, M., Aiba, A. and Saito, N.
  • Organizer: The 37th Naito Conference,
  • Place of Presentation: 北海道ニセコ
  • Year and Date: 2014-07-15 – 2014-07-18