<最近のおもな招待講演-Resent Invited Presentations>

K Muraki, Approach of critical amino acid identification of TRP channels: Integration of computer science and experimental benchwork. CFS/ME International 2023: RID - Research Innovation and Discovery Conference (Keynote speaker, 9-10, Nov., 2023, Kings Cliff, Australia)

 

K Muraki, Comparison of TRPA1 and PIEZO1 channel functions among species. Ion Channel Modulation Symposium (ICMS), (22nd/23rd June, 2022, Clare College Cambridge, UK)

 

K Muraki, うつ病・不安症に対する扁桃体の関与とその神経基盤-TRPC1/4/5サブファミリーの生理機能と精神疾患への関与. 第14回日本不安症学会学術大会 ランチョンセミナー2(2022521日、東京)

 

K Muraki, PIEZO Channels as a sensor for mechanical stress. CFS/ME International 2021: RID - Research Innovation and Discovery Conference (Keynote speaker, 16-17, Nov., 2021, Gold Coast, Australia)

K Muraki, ストレスセンサーとして働くTRPチャネルとPIEZOチャネル. JT社 製品評価センター講演会 (20201, 横浜)

K Muraki, TRP channels and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Overview and Future Perspectives. CFS/ME International 2018: RID - Research Innovation and Discovery Conference (26-27, Nov., 2018, Gold Coast, Australia)

K Muraki, TRP channels in arthritis, Scandinavian Congress of Rheumatology (Sept., 2018, Helsinki, Finland)

K Muraki, 薬物の作用点としてのカチオンチャネル:その多様性から新たな視点を探る. 2014年度 京都薬科大学 創薬科学フロンテフィアシンポジウム (201411, 京都)

K Muraki, Transcriptional regulation of TRPA1 channel: Links between inflammation and channel expression, Finish Pharmacological Society, Annual meeting 2014 (Apr., 2014, Tampere, Finland)

 

<最近のおもな発表論文-Main Publications>

2024

M Matsubara, Y Muraki, H Suzuki, N Hatano & K Muraki. Critical Amino Acid Residues Regulating TRPA1 Zn2+ Response: A Comparative Study Across Species. J. Biol. Chem. in Press (2024).

2022

M Matsubara, Y Muraki, N Hatano, H Suzuki & K Muraki. Potent Activation of Human but Not Mouse TRPA1 by JT010. Int. J. Mol. Sci. 23(22), 1429, (2022).

2021 

N Hatano, M Matsubara, H Suzuki, Y Muraki & K Muraki. HIF-1α dependent upregulation of ZIP8, ZIP14, and TRPA1 modify intracellular Zn2+ accumulation in inflammatory synoviocytes. Int. J. Mol. Sci. 22(12), 6349 (2021). (Based on research from 2011 to 2015)

2020

村木克彦, 今泉祐治. TRPC145チャネルの生理機能および疾病との関連と標的創薬―特異的な活性化薬・抑制薬の発見による研究展開. Physiological functions and pathophysiological aspects of TRPC1/4/5 channels and drug discovery targeting on them. 別冊・医学のあゆみ TRPチャネルのすべて 25-31 (2020).

2019

M Yoneda, H Suzuki, N Hatano, S Nakano, Y Muraki, K Miyazawa, S Goto & K Muraki. PIEZO1 and TRPV4, which are distinct mechano-sensors in the osteoblastic MC3T3-E1 cells, modify the cell-proliferation. Int. J. Mol. Sci. 20 (19), e4960 (2019). Top Downloaded Papers 2019

Keypoint & 臨床との接点:マウス骨芽細胞で機械刺激受容PIEZO1チャネルTRPV4チャネルが機能連関し、骨芽細胞の増殖を制御することを明らかにしました!!

 

村木克彦, 今泉祐治. TRPC145チャネルの生理機能および疾病との関連と標的創薬―特異的な活性化薬・抑制薬の発見による研究展開. Physiological functions and pathophysiological aspects of TRPC1/4/5 channels and drug discovery targeting on them. 医学のあゆみ 270 (10). 889-895 (2019).

2018

T Suzuki#, Y Muraki##, N Hatano##, H Suzuki## & K Muraki#. PIEZO1 channel is a potential regulator of synovial sarcoma cell-viability. Int. J. Mol. Sci. 19 (5), e1452 (2018). #, ##: equal contributions

Keypoint & 臨床との接点:機械刺激受容PIEZO1チャネルがヒト滑膜肉腫の細胞活性を制御する可能性を見出しました!!

2017

K Muraki, K Ohnishi, A Takezawa, H Suzuki, N Hatano, Y Muraki, N Hamzah, R Foster, H Waldmann, P Nussbaumer, M Christmann, RS Bon & DJ Beech. Na+ entry through heteromeric TRPC4/C1 channels mediates (-)Englerin A-induced cytotoxicity in synovial sarcoma cells. Sci. Rep. 7 (1), 16988 (2017).

Keypoint & 臨床との接点:(-)-Englerin ATRPC1/C4チャネルヘテロマを活性化し、ヒト滑膜肉腫に抗がん作用を及ぼすことを見出しました!!

 

K Muraki, T Sekine, Y Ando, H Suzuki, N Hatano, T Hirata & Y Muraki. An environmental pollutant, 9,10-phenanthrenequinone, activates human TRPA1 via critical cysteines 621 and 665. Pharmacol. Res. & Persp. 5, e00342 (2017).

Keypoint & 臨床との接点:環境汚染物質9,10-フェナンスレンキノンの短期曝露がTRPA1チャネルの活性化を介して、気道系組織の生理機能に影響する可能性を見出しました!!

2016

H Suzuki*, E Sasaki#, A Nakagawa#, Y Muraki, N Hatano & K Murak*. Diclofenac, a non-steroidal anti-inflammatory drug, is an antagonist of human TRPM3 isoforms. Pharmacol. Res. & Persp. 4, e00232 (2016). *, #: equal contributions

Keypoint & 臨床との接点:鎮痛薬として汎用されるジクロフェナク(ボルタレン)がTRPM3チャネルの阻害作用を有することが明らかになりました!!

2015

K. Muraki, N. Hatano*, H. Suzuki*, Y Muraki*, Y. Iwajima, Y. Maeda & H. Ono. Oseltamivir blocks human neuronal nicotinic acetylcholine receptor-mediated currents. Basic Clin. Pharmacol. Toxicol., 11687-95 (2015). *: equal contributions

Keypoint & 臨床との接点:抗インフルエンザ薬のタミフルがヒトのニコチン性アセチルコリン受容体チャネルを直接抑制するが明らかになりました!!

2014

K. Muraki & H. Ono. Human nicotinic acetylcholine receptor is a potential pharmacological target of oseltamivir. Receptors & Clin. Invest. Research Highlight, 1, e360 (2014).

 

H. Suzuki, N. Hatano, Y. Muraki, Y. Itoh, S. Kimura, H. Hayashi, K. Onozaki, Y. Ohi, A. Haji & K. Muraki. The NADPH oxidase inhibitor diphenyleneiodonium activates the human TRPA1 nociceptor. Am. J. Physiol., Cell-Physiol. 307, C384-C397 (2014).

 

<共同研究論文-Collaborative Publications>

2024

Etianne Martini Sasso, Katsuhiko Muraki, Natalie Eaton-Fitch, Peter K. Smith, Andrew Jeremijenko, Paul Griffin, Sonya Marshall-Gradisnik. Investigation into the restoration of TRPM3 ion channel activity in post COVID-19 condition: a potential pharmacotherapeutic target. Front. Immunol. in Press (2024).

2022

E M Sasso, K Muraki, N Eaton-Fitch P Smith, O L Lesslar, G Deed, S Marshall-Gradisnik. Transient receptor potential melastatin 3 dysfunction in post COVID-19 condition and myalgic encephalomyelitis/chronic fatigue syndrome patients. Mol. Med.;28(1):98 (2022).

 

N Eaton-Fitch, S D Preez, H Cabanas, K Muraki, D Staines, S Marshall-Gradisnik. Impaired TRPM3-dependent calcium influx and restoration using Naltrexone in natural killer cells of myalgic encephalomyelitis/chronic fatigue syndrome patients. J. Trans. Med. 20, 94 (2022).

2021 

S Luostarinen, M Hämäläinen, N HatanoK Muraki, E Moilanen. The Inflammatory Regulation of TRPA1 Expression in Human A549 Lung Epithelial Cells. Pulm. Pharmacol. Ther. 70, 102059 (2021).

H Cabanas, K Muraki, N Eaton-Fitch, D Staines & S Marshall-Gradisnik. Potential therapeutic benefit of Low Dose Naltrexone in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Role of Transient Receptor Potential Melastatin 3 ion channels in pathophysiology and treatment. Front. Immunol., 12: 687806 (2021).

2019

H Cabanas, K Muraki, D Staines & S Marshall-Gradisnik. Naltrexone restores impaired transient receptor potential melastatin 3 ion channel function in natural killer cells from myalgic encephalomyelitis/chronic fatigue syndrome patients. Front. Immunol., 10: 2545 (2019).

Keypoint & 臨床との接点:慢性疲労症候群(CFS/ME)患者のNK細胞で観察されたTRPM3チャネル機能の低下がNaltrexoneで一部回復する可能性を見出しました!!

 

NM Blythe, K Muraki, MJ Ludlow, V Stylianidis, HTJ Gilbert, EL Evans, K Cuthbertson, R Foster, J Swift, J Li, MJ Drinkhill, FA van Nieuwenhoven, KE. Porter, DJ Beech & NA Turner.  Mechanically-activated Piezo1 channels of cardiac fibroblasts stimulate p38 mitogen-activated protein kinase and interleukin-6 secretion. J. Biol. Chem., 294 (46), 17395-17408 (2019).

Keypoint & 臨床との接点:機械刺激受容PIEZO1チャネルが心筋線維芽細胞に機能発現し、その活性化がp38MAPKを介してIL-6 産生を制御することを見出しました!!

 

V Deivasikamani, S Dhayalan, Y Abudushalamu, R Mughal, A Visnagri, K Cuthbertson, JL Scragg, TS Munsey, H Viswambharan, K Muraki, R Foster, A Sivaprasadarao, MT Kearney, DJ Beech & P Sukumar. Piezo1 channel activation mimics high glucose as a stimulator of insulin release. Sci. Rep., 9 (1), 16876 (2019).

Keypoint & 臨床との接点:機械刺激受容PIEZO1チャネルが膵臓β細胞からのインスリン分泌を制御する可能性を見出しました!!

 

A Minard, CC Bauer, EC Bon, IB Pickles, DJ Wright, MJ Ludlow, MP Burnham, SL Warriner, DJ Beech, K Muraki* & RS Bon*. Potent, selective and subunit-dependent activation of TRPC5 channels by a xanthine derivative. Brit. J. Pharmacol., 176, 3924-3938 (2019). Top downloaded paper 2018-2019. *Corresponding Authors

Keypoint & 臨床との接点:新規のPico145誘導体AM237がホモマー型TRPC5チャネルを特異的に活性化することを見出しました!! Brit J Pharmacol.Top Downloaded Paper 2018-2019の一つに選ばれました)

 

Ohya S, Ito K, Hatano N, Ohno A, Muraki KImaizumi Y. Castration Induces Down-Regulation of A-Type K+ Channel in Rat Vas Deferens Smooth Muscle. Int. J. Mol. Sci. 20 (17), e4047 (2019).

 

I Mäki-Opas, M Hämäläinen, LJ Moilanen, R Haavikko, TJ Ahonen, S Alakurtti, VM Moreira, K Muraki, J Yli-Kauhaluoma & E Moilanen. Pyrazine-fused triterpenoids block the TRPA1 ion channel in vitro and inhibit TRPA1-mediated acute inflammation in vivo. ACS Chem Neurosci. 10, 2848-2857 (2019).

Keypoint & 臨床との接点:白樺に含まれるトリテルペノイド骨格を持つ新規TRPA1チャネル阻害薬を見出し、これが関節の炎症性浮腫を抑制することを明らかにしました!!

 

H Cabanas, K Muraki, C Balinas, N Eaton-Fitch, D Staines & S Marshall-Gradisnik. Validation of impaired Transient Receptor Potential Melastatin 3 ion channel activity in Natural Killer cells from Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis patients. Mol. Med. 25 (1), 14 (2019).

Keypoint & 臨床との接点:臨床で用いられている薬物を使って、慢性疲労症候群(CFS/ME)患者のNK細胞でTRPM3チャネル機能が低下していることを確認しました!!

 

T Sekine, T Hirata, S Ishikawa, S Ito, K Ishimori, K Matsumura & K Muraki. Regulation of NRF2, AP-1, and NF-κB by cigarette smoke exposure in three-dimensional human bronchial epithelial cells. J. Appl. Toxicol. 39, 717-725 (2019).

2018

H Cabanas, K Muraki, N Eaton, C Balinas, D Staines & S Marshall-Gradisnik. Loss of Transient Receptor Potential Melastatin 3 ion channel function in natural killer cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients. Mol Med., 24 (1), 44 (2018).

Keypoint & 臨床との接点:慢性疲労症候群(CFS/ME)患者のNK細胞でTRPM3チャネル機能が低下していることを見出しました!!

 

A Minard, CC Bauer, DJ Wright, HN Rubaiy, K Muraki, DJ Beech & RS Bon. Remarkable progress with small-molecule modulation of TRPC1/4/5 channels: Implications for understanding the channels in health and disease. Cells 7 (6), e52 (2018). Review Article

 

Hatano N, Ohya S, Imaizumi Y, Clark RB, Belke D, Giles WR. ATP increases [Ca2+]i and activates a Ca2+ -dependent Cl- current in rat ventricular fibroblasts. Exp Physiol., 103 (5), 666-682 (2018).

2017

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*. Picomolar, selective and subtype specific small-molecule inhibition of TRPC1/4/5 channels. J. Biol. Chem. 292, 8158-8173 (2017). *Corresponding Authors

Keypoint & 臨床との接点:TRPC1/C4/C5チャネルヘテロマを極めて強力に阻害する薬物(Pico145と命名)を初めて見出し、TRPC1/4/5の生理機能を明らかにしました!!

 

K Sakamoto, Y Suzuki, H Yamamura, S Ohya, K Muraki & Y Imaizumi, Molecular mechanisms underlying pimaric acid-induced modulation of voltage-gated K+ channels. J. Pharmacol Sci., 133, 223-231 (2017).

 

MJ Ludlow, HJ Gaunt, HN Rubaiy, KE Musialowski, NM Blythe, NS Vasudev, K Muraki & DJ Beech, (-)-Englerin A-evoked Cytotoxicity is Mediated by Na+ Influx and Counteracted by Na+ /K+-ATPase. J. Biol. Chem. 292, 723-731 (2017).

Keypoint & 臨床との接点:(-)-Englerin Aの抗がん作用には、TRPC1/C4チャネルの活性化を介したがん細胞へのNa+負荷が重要であることが明らかになりました!!

 

M Fujimoto, T Inoue, H Kito, S Niwa, T Suzuki, K Muraki & S Ohya, Transcriptional repression of HER2 by ANO1 Cl- channel inhibition in human breast cancer cells with resistance to trastuzumab. Biochem. Biophys. Res. Comm. 482, 188-194 (2017).

2016

S. Ohya*, H. Kito, N. Hatano & K. Muraki*, Recent advances in therapeutic strategies that focus on the regulation of ion channel expression. Pharmacol & Therap 160, 11-43 (2016). Review Article, *Corresponding Authors

 

S. Ohya, S. Kanatsuka, N. Hatano, H. Kito, A. Matsui, M. Fujimoto, S. Matsuba, S. Niwa, P. Zhan, T. Suzuki & K. Muraki, Downregulation of the Ca2+-activated K+ channel KCa3.1 by histone deacetylase inhibition in human breast cancer cells. Pharmacol. Res. & Persp. 4, e00228 (2016).

 

Moilanen LJ, Hämäläinen M, Lehtimäki L, Nieminen RM, Muraki K & Moilanen E. Pinosylvin Inhibits TRPA1-Induced Calcium Influx In Vitro and TRPA1-Mediated Acute Paw Inflammation In Vivo. Basic Clin. Pharmacol. Toxicol. 118, 238-242 (2016).

Keypoint & 臨床との接点:松に含まれる生薬成分のピノシルビンがTRPA1チャネルの阻害作用を介して関節の炎症性浮腫を抑制することが明らかになりました!!

 

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. Natural and synthetic flavonoid modulation of TRPC5 channels. Brit. J. Pharmacol., 173, 562-574 (2016).

Keypoint & 臨床との接点:プロポリスなどに含まれる生薬成分のガランジン(ガランギン)およびその新規誘導物質がTRPC4TRPC5チャネル阻害作用を有することを明らかにしました!!

2015

Y. Akbulut, H. Gaunt, K. Muraki, M. Ludlow, M. Amer, A. Bruns, N. Vasudev, L. Radtke, M. Willot, S. Hahn, T. Seitz, S. Ziegler, M. Christmann, D.  Beech & H. Waldmann.  (-)-Englerin A is a potent and selective activator of TRPC4 and TRPC5 calcium channels. Angewandte Chemie Int. Ed., 54, 3787-3791 (2015). Hot paper

Keypoint & 臨床との接点:アフリカ産植物由来の(-)-Englerin ATRPC4チャネルの活性化を介して選択的に腎がんを抑制することが明らかになりました!!Innovations Report, Spotlight in ACS chemical biology, Chemical & Engineering Newsでも紹介されています)

2014

Li J, Hou B, Tumova S, Muraki K, Bruns A, et al. Piezo1 integration of vascular architecture with physiological force. Nature, 515, 279-282 (2014).

Keypoint & 臨床との接点:PIEZO1チャネルが血管内皮の力覚応答を介して血管発生に関わることが明らかになりました!!

 

S. Matsuba, S. Niwa, K. Muraki, S. Kanatsuka, Y. Nakazono, N. Hatano, M. Fujii, P. Zhan, T. Suzuki & S. Ohya. Downregulation of Ca2+-activated Cl- channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells. J. Pharmacol. Exp. Therap., 351, 510-518 (2014).