Transcriptional regulation of cation channels by iPS factors and the expression deficient diseases

• Project/Area Number: 26460349
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Aichi Gakuin University
• Principal Investigator: Muraki Katsuhiko 愛知学院大学, 薬学部, 教授 (20254310)
• Co-Investigator(Kenkyū-buntansha): 鈴木 裕可 愛知学院大学, 薬学部, 助教 (00581026) ; 波多野 紀行 愛知学院大学, 薬学部, 講師 (50454319)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: iPS / カチオンチャネル / 転写 / iPS因子 / TRPチャネル / 細胞分化 / チャネル / TRP

Outline of Final Research Achievements

We here examined effects of iPS factors, Sox2 and Klf4, on expression of TRP channels in HEK cells where iPS factors were hetelorogously expressed. Sox2 induced the expression of TRPC6, TRPM1, TRPM2, and TRPV2, whereas it reduced the expression of TRPA1. On the other hand, Klf4 induced the marked expression of TRPC5, TRPC6, TRPM2, TRPM4, TRPM6, and TRPV2, whereas it reduced the expression of TRPC1. These results suggest that iPS factors, Sox2 and Klf4, regulate gene-expression of ion channels. In this study, we also demonstrate that differentiation of non-neuronal cell line neuroblastorma to neuron induces functional expression of TRPM3.

Research Products

• [Journal Article] Transcriptional repression of HER2 by ANO1 Cl- channel inhibition in human breast cancer cells with resistance to trastuzumab. (2017)
  • Author(s): M. Fujimoto, T. Inoue, H. Kito, S. Niwa, T. Suzuki, K. Muraki & S. Ohya
  • Journal Title: Biochem. Biophys. Res. Comm. Volume: 482 Issue: 1 Pages: 188-194
  • DOI: 10.1016/j.bbrc.2016.11.033
  • Peer Reviewed / Open Access
• [Journal Article] (-)-Englerin A-evoked Cytotoxicity is Mediated by Na+ Influx and Counteracted by Na+ /K+-ATPase. (2017)
  • Author(s): MJ Ludlow, HJ Gaunt, HN Rubaiy, KE Musialowski, NM Blythe, NS Vasudev, K Muraki & DJ Beech
  • Journal Title: J. Biol. Chem. Volume: 292 Issue: 2 Pages: 723-731
  • DOI: 10.1074/jbc.m116.755678
  • Peer Reviewed
• [Journal Article] Molecular mechanisms underlying pimaric acid-induced modulation of voltage-gated K+ channels. (2017)
  • Author(s): Sakamoto K, Suzuki Y, Yamamura H, Ohya S, Muraki K, Imaizumi Y.
  • Journal Title: J Pharmacol Sci. Volume: 印刷中 Issue: 4 Pages: 223-231
  • DOI: 10.1016/j.jphs.2017.02.013
  • Peer Reviewed / Open Access
• [Journal Article] Picomolar, selective and subtype specific small-molecule inhibition of TRPC1/4/5 channels. (2017)
  • Author(s): Rubaiy HN, Ludlow MJ, Henrot M, Gaunt HJ, Miteva K, Cheung SY, Tanahashi Y, Hamzah N, Musialowski KE, Blythe NM, Appleby HL, Bailey MA, McKeown L, Taylor R, Foster R, Waldmann H, Nussbaumer P, Christmann M, Bon RS, Muraki K* & Beech DJ*
  • Journal Title: J. Biol. Chem. Volume: 印刷中 Issue: 20 Pages: 8158-8173
  • DOI: 10.1074/jbc.m116.773556
  • Peer Reviewed / Open Access
• [Journal Article] Diclofenac, a non-steroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms. (2016)
  • Author(s): H Suzuki, E Sasaki, A Nakagawa, Y Muraki, N Hatano & K Murak
  • Journal Title: Pharmacol Res & Persp Volume: 4(3) Issue: 3
  • DOI: 10.1002/prp2.232
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Natural and synthetic flavonoid modulation of TRPC5 channels. (2016)
  • Author(s): J Naylor, A Minard, H Gaunt, M Amer, L Wilson, M Migliore, S Cheung, H Rubaiy, N Blythe, K Musialowski, M Ludlow, W Evans, B Green, H Yang, Y You, J Li, C Fishwick, K Muraki, D Beech & R Bon.
  • Journal Title: Brit. J. Pharmacol. Volume: 173 Issue: 3 Pages: 562-574
  • DOI: 10.1111/bph.13387
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pinosylvin Inhibits TRPA1-Induced Calcium Influx In Vitro and TRPA1-Mediated Acute Paw Inflammation In Vivo. (2016)
  • Author(s): Moilanen LJ, Hämäläinen M, Lehtimäki L, Nieminen RM, Muraki K & Moilanen E.
  • Journal Title: Basic Clin. Pharmacol. Toxicol. Volume: 118 Issue: 3 Pages: 238-242
  • DOI: 10.1111/bcpt.12485
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Downregulation of the Ca2+-activated K+ channel KCa3.1 by histone deacetylase inhibition in human breast cancer cells. (2016)
  • Author(s): Ohya, S Kanatsuka, N Hatano, H Kito, A Matsui, M Fujimoto, S Matsuba, S Niwa, P Zhan, T Suzuki & K Muraki.
  • Journal Title: Pharmacol Res & Persp Volume: 4(2) Issue: 2
  • DOI: 10.1002/prp2.228
  • Peer Reviewed / Open Access
• [Journal Article] Recent advances in therapeutic strategies that focus on the regulation of ion channel expression. (2016)
  • Author(s): Ohya, H. Kito, N. Hatano & K. Muraki.
  • Journal Title: Pharmacol & Therap Volume: 160 Pages: 11-43
  • Peer Reviewed / Open Access
• [Journal Article] (-)-Englerin A is a Potent and Selective Activator of TRPC4 and TRPC5 Calcium Channels. (2015)
  • Author(s): Akbulut Y, Gaunt HJ, Muraki K, Ludlow MJ, Amer MS, Bruns A, Vasudev NS, Radtke L, Willot M, Hahn S, Seitz T, Ziegler S, Christmann M, Beech DJ, Waldmann H.
  • Journal Title: Angew Chem Int Ed Engl Volume: 54 Issue: 12 Pages: 3787-3791
  • DOI: 10.1002/anie.201411511
  • Peer Reviewed
• [Journal Article] Oseltamivir blocks human neuronal nicotinic acetylcholine receptor-mediated currents. (2015)
  • Author(s): Muraki K, Hatano N, Suzuki H, Muraki Y, Iwajima Y, Maeda Y, Ono H.
  • Journal Title: Basic Clin Pharmacol Toxicol. Volume: 116 Issue: 2 Pages: 87-95
  • DOI: 10.1111/bcpt.12290
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells (2015)
  • Author(s): Matsuba S, Miwa S, Muraki K, Kanatsuka S, Nakazuno Y, Hatano N, Fujii M, Zhan P, Suzuki T, Ohya S
  • Journal Title: Journal of Pharmacology & Experimental Therapeutics Volume: 351 Issue: 3 Pages: 510-518
  • DOI: 10.1124/jpet.114.217315
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Piezo1 integration of vascular architecture with physiological force. (2014)
  • Author(s): Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, Yuldasheva NY, Majeed Y, Wilson LA, Rode B, Bailey MA, Kim HR, Fu Z, Carter DA, Bilton J, Imrie H, Ajuh P, Dear TN, Cubbon RM, Kearney MT, Prasad KR, Evans PC, Ainscough JF, Beech DJ.
  • Journal Title: Nature Volume: 515 Issue: 7526 Pages: 279-282
  • DOI: 10.1038/nature13701
  • Peer Reviewed / Open Access
• [Journal Article] The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1 nociceptor. (2014)
  • Author(s): Hiroka Suzuki, Noriyuki Hatano, Yukiko Muraki, Yuka Itoh, Satoko Kimura, Hidetoshi Hayashi, Kikuo Onozaki, Yoshiaki Ohi, Akira Haji, Katsuhiko Muraki
  • Journal Title: American Journal of Physiology -Cell Physiology Volume: 307 Issue: 4 Pages: C384-C394
  • DOI: 10.1152/ajpcell.00182.2013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Remarks] Cellular Pharmacology
  • URL: http://www.phar.agu.ac.jp/lab/cell_pharm/cellpharmacol.html
• [Remarks] 薬効解析学 Cellular Pharmacology
  • URL: http://www.phar.agu.ac.jp/lab/cell_pharm/cellpharmacol.html