リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Open channel block of Kv1.5 channels by HMQ1611」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Open channel block of Kv1.5 channels by HMQ1611

DONG Chao LI Jiawei DING Wei-guang 80242973 0000-0001-6710-5489 UEDA Rika XIE Xiaolu WU Jie MATSUURA Hiroshi 60238962 0000-0003-1998-0996 HORIE Minoru 90183938 0000-0002-9029-2339 滋賀医科大学

2022.09.16

概要

Kv1.5 channels conduct the ultra-rapid delayed rectifier potassium current (I Kur). Pharmacological blockade of human Kv1.5 (hKv1.5) has been regarded as an effective treatment of re-entrant based atrial fibrillation, because Kv1.5 is highly expressed in human cardiac atria but scarcely in ventricles. The Kv1.5 blockade is also expected to be used in cancer therapeutics since Kv1.5 is overexpressed in some types of human tumors. Here, we investigated the blockade of hKv1.5 channels by HMQ1611, a symmetrical biphenyl derivative. hKv1.5 channels were heterologously expressed in Chinese hamster ovary cells. The effects of HMQ1611 on wild-type and 13 hKv1.5 mutant channels were examined using the whole-cell patch-clamp method, and molecular docking simulation was conducted to predict the docking position of HMQ1611 within Kv1.5 channels. We showed that HMQ1611 reversibly inhibited the hKv1.5 current in a concentration-dependent manner (IC50 = 2.07 μM). HMQ1611 blockade of hKv1.5 current developed with time during depolarizing voltage-clamp steps, and this blockade was also voltage-dependent with a steep increase over the voltage range for channel openings. HMQ1611 inhibition was significantly reduced in the T479A, T480A, V505A, I508A, L510A, V512A, and V516A hKv1.5 mutant channels. Molecular docking analysis predicted that V505, V512, and T480 were involved in the blocking action of HMQ1611 on hKv1.5 channels. These results suggest that HMQ1611 inhibits hKv1.5 currents as an open channel blocker. Amino acid residues located at the base of the selectivity filter (T479 and T480) and in the S6 segment (V505, I508, L510, V512, and V516) of hKv1.5 appear to constitute potential binding sites for HMQ1611.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

Attali, B., Chandy, K. G., Giese, M. H., Grissmer, S., Gutman, G. A., Jan, L. Y., et al. (2019). Voltage-gated potassium channels (version 2019.4) in the IUPHAR/BPS Guide to pharmacology database. IUPHAR. BPS. Guide Pharm. CITE 2019 (4), 1–48. doi:10.2218.gtopdb/F81.2019.4

Aung, T., Asam, C., and Haerteis, S. (2019). Ion channels in sarcoma: Pathophysiology and treatment options. Pflugers Arch. 471 (9), 1163–1171. doi:10.1007/s00424-019-02299-8

Bai, J. Y., Ding, W. G., Kojima, A., Seto, T., and Matsuura, H. (2015). Putative binding sites for arachidonic acid on the human cardiac Kv1.5 channel. Br. J. Pharmacol. 172 (22), 5281–5292. doi:10.1111/bph.13314

Bielanska, J., Hernández-Losa, J., Pérez-Verdaguer, M., Moline, T., Somoza, R., Ramon, Y. C. S., et al. (2009). Voltage-Dependent potassium channels Kv1.3 and Kv1.5 in human cancer. Curr. Cancer Drug Targets 9 (8), 904–914. doi:10.2174/ 156800909790192400

Borrego, J., Feher, A., Jost, N., Panyi, G., Varga, Z., and Papp, F. (2021). Peptide inhibitors of Kv1.5: An option for the treatment of atrial fibrillation. Pharm. (Basel) 14 (12), 1303. doi:10.3390/ph14121303

Brown, R. A., Lau, Y. C., and Lip, G. Y. (2014). Vernakalant hydrochloride to treat atrial fibrillation. Expert Opin. Pharmacother. 15 (6), 865–872. doi:10.1517/14656566.2014.898751

Burashnikov, A., Pourrier, M., Gibson, J. K., Lynch, J. J., and Antzelevitch, C. (2012). Rate-dependent effects of vernakalant in the isolated non-remodeled canine left atria are primarily due to block of the sodium channel: Comparison with ranolazine and dl-sotalol. Circ. Arrhythm. Electrophysiol. 5 (2), 400–408. doi:10. 1161/CIRCEP.111.968305

Chen, R., and Chung, S. H. (2018). Inhibition of voltage-gated K+ channel Kv1.5 by antiarrhythmic drugs. Biochemistry 57 (18), 2704–2710. doi:10.1021/acs. biochem.8b00268

Chiamvimonvat, N., Chen-Izu, Y., Clancy, C. E., Deschenes, I., Dobrev, D., Heijman, J., et al. (2017). Potassium currents in the heart: Functional roles in repolarization, arrhythmia and therapeutics. J. Physiol. 595 (7), 2229–2252. doi:10.1113/JP272883

Christophersen, I. E., Olesen, M. S., Liang, B., Andersen, M. N., Larsen, A. P., Nielsen, J. B., et al. (2013). Genetic variation in KCNA5: Impact on the atrial specific potassium current IKur in patients with lone atrial fibrillation. Eur. Heart J. 34 (20), 1517–1525. doi:10.1093/eurheartj/ehs442

Comes, N., Bielanska, J., Vallejo-Gracia, A., Serrano-Albarras, A., Marruecos, L., Gomez, D., et al. (2013). The voltage-dependent K(+) channels Kv1.3 and Kv1.5 in human cancer. Front. Physiol. 4, 283. doi:10.3389/fphys.2013.00283

Comes, N., Serrano-Albarras, A., Capera, J., Serrano-Novello, C., Condom, E., Ramon, Y. C. S., et al. (2015). Involvement of potassium channels in the progression of cancer to a more malignant phenotype. Biochim. Biophys. Acta 1848 (10), 2477–2492. doi:10.1016/j.bbamem.2014.12.008

Decher, N., Kumar, P., Gonzalez, T., Pirard, B., and Sanguinetti, M. C. (2006). Binding site of a novel Kv1.5 blocker: A "foot in the door" against atrial fibrillation. Mol. Pharmacol. 70 (4), 1204–1211. doi:10.1124/mol.106. 026203

Ebrahimi, S., Hosseini, M., Shahidsales, S., Maftouh, M., Ferns, G. A., Ghayour-Mobarhan, M., et al. (2017). Targeting the Akt/PI3K signaling pathway as a potential therapeutic strategy for the treatment of pancreatic cancer. Curr. Med. Chem. 24 (13), 1321–1331. doi:10.2174/0929867324666170206142658

Ei-Haou, S., Ford, J. W., and Milnes, J. T. (2015). Novel K+ channel targets in atrial fibrillation drug development-where are we? J. Cardiovasc. Pharmacol. 66 (5), 412–431. doi:10.1097/FJC.0000000000000277

Eldstrom, J., Wang, Z., Xu, H., Pourrier, M., Ezrin, A., Gibson, K., et al. (2007). The molecular basis of high-affinity binding of the antiarrhythmic compound vernakalant (RSD1235) to Kv1.5 channels. Mol. Pharmacol. 72 (6), 1522–1534. doi:10.1124/mol.107.039388

Fedida, D., Wible, B., Wang, Z., Fermini, B., Faust, F., Nattel, S., et al. (1993). Identity of a delayed rectifier current from human heart with a cloned K+ channel current. Circ. Res. 73 (1), 210–216. doi:10.1161/01.res.73.1.210

Felipe, A., Bielanska, J., Comes, N., Vallejo, A., Roig, S., Ramon, Y. C. S., et al. (2012). Targeting the voltage-dependent K+ channels Kv1.3 and Kv1.5 as tumor biomarkers for cancer detection and prevention. Curr. Med. Chem. 19 (5), 661–674. doi:10.2174/092986712798992048

Fukushima, Y., Kojima, A., Mi, X., Ding, W. G., Kitagawa, H., and Matsuura, H. (2020). Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated Kv1.5 channel. Br. J. Pharmacol. 177 (16), 3811–3827. doi:10.1111/bph.15105

Geng, M., Lin, A., and Nguyen, T. P. (2020). Revisiting antiarrhythmic drug therapy for atrial fibrillation: Reviewing lessons learned and redefining therapeutic paradigms. Front. Pharmacol. 11, 581837. doi:10.3389/fphar. 2020.581837

Heijman, J., Sutanto, H., Crijns, H. J. G. M., Nattel, S., and Trayanova, N. A. (2021). Computational models of atrial fibrillation: Achievements, challenges, and perspectives for improving clinical care. Cardiovasc. Res. 117 (7), 1682–1699. doi:10. 1093/cvr/cvab138

Kojima, A., Ito, Y., Ding, W. G., Kitagawa, H., and Matsuura, H. (2015). Interaction of propofol with voltage-gated human Kv1.5 channel through specific amino acids within the pore region. Eur. J. Pharmacol. 764, 622–632. doi:10.1016/j.ejphar.2015.08.007

Lee, H. M., Hahn, S. J., and Choi, B. H. (2016). Blockade of Kv1.5 channels by the antidepressant drug sertraline. Korean J. Physiol. Pharmacol. 20 (2), 193–200. doi:10.4196/kjpp.2016.20.2.193

Lu, W., Dai, B., Ma, W., and Zhang, Y. (2012). A novel taspine analog, HMQ1611, inhibits growth of nonsmall cell lung cancer by inhibiting angiogenesis. Oncol. Lett. 4 (5), 1109–1113. doi:10.3892/ol.2012.855

Nattel, S., Heijman, J., Zhou, L., and Dobrev, D. (2020). Molecular basis of atrial fibrillation pathophysiology and therapy: A translational perspective. Circ. Res. 127 (1), 51–72. doi:10.1161/CIRCRESAHA.120.316363

Peyronnet, R., and Ravens, U. (2019). Atria-selective antiarrhythmic drugs in need of alliance partners. Pharmacol. Res. 145, 104262–104102. doi:10.1016/j.phrs. 2019.104262

Ravens, U., and Odening, K. E. (2017). Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers. Pharmacol. Ther. 176, 13–21. doi:10.1016/j.pharmthera.2016.10.003

Serrano-Novillo, C., Capera, J., Colomer-Molera, M., Condom, E., Ferreeres, J. C., and Felipe, A. (2019). Implication of voltage-gated potassium channels in neoplastic cell proliferation. Cancers (Basel) 11 (3), 287. doi:10.3390/cancers11030287

Sun, H., Oudit, G. Y., Ramirez, R. J., Costantini, D., and Backx, P. H. (2004). The phosphoinositide 3-kinase inhibitor LY294002 enhances cardiac myocyte contractility vis a direct inhibition of Ik, slow currentys. Cardiovasc. Res. 62 (3), 509–520. doi:10.1016/j.cardiores.2004.01.029

Tikhonov, D. B., and Zhorov, B. S. (2014). Homology modeling of Kv1.5 channel block by cationic and electroneutral ligands. Biochim. Biophys. Acta 1838 (3), 978–987. doi:10.1016/j.bbamem.2013.11.019

Villalonga, N., Martinez-Marmol, R., Roura-Ferrer, M., David, M., Valenzuela, C., Soler, C., et al. (2008). Cell cycle-dependent expression of Kv1.5 is involved in myoblast proliferation. Biochim. Biophys. Acta 1783 (5), 728–736. doi:10.1016/j. bbamcr.2008.01.001

Vlahos, C. J., Matter, W. F., Hui, K. Y., and Brown, R. F. (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1- benzopyran-4-one (LY294002). J. Biol. Chem. 269, 5241–5248. doi:10.1016/ S0021-9258(17)37680-9

Voigt, N., and Dobrev, D. (2016). Atrial-selective potassium channel blockers. Card. Electrophysiol. Clin. 8 (2), 411–421. doi:10.1016/j.ccep.2016. 02.005

Wijesurendra, R. S., and Casadei, B. (2019). Mechanisms of atrial fibrillation. Heart 105 (24), 1860–1867. doi:10.1136/heartjnl-2018-314267

Woodhull, A.M. (1973). Ion blockage of sodium channels in nerve. J.Gen. Physiol. 61 (6), 687–708. doi:10.1085/jpg/61.6.687

Wu, J., Chen, Z., Liu, Q., Zeng, W., Wu, X., and Lin, B. (2015). Silencing of Kv1.5 gene inhibits proliferation and induces apoptosis of osteosarcoma cells. Int. J. Mol. Sci. 16 (11), 26914–26926. doi:10.3390/ijms161126002

Wu, J., Ding, W. G., Matsuura, H., Tsuji, K., Zang, W. J., and Horie, M. (2009). Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the human Kv1.5 channel. Br. J. Pharmacol. 156 (2), 377–387. doi:10.1111/j.1476-5381. 2008.00017.x

Wu, W., and Sanguinetti, M. C. (2016). Molecular basis of cardiac delayed rectifier potassium channel function and pharmacology. Card. Electrophysiol. Clin. 8 (2), 275–284. doi:10.1016/j.ccep.2016.01.002

Zhan, Y., Zhang, Y., Liu, C., Zhang, J., Smith, W. W., Wang, N., et al. (2012). A novel taspine derivative, HMQ1611, inhibits breast cancer cell growth via estrogen receptor α and EGF receptor signaling pathways. Cancer Prev. Res. (Phila). 5 (6), 864–873. doi:10.1158/1940-6207.CAPR-11-0575

Zhang, J., Zhang, Y. M., Pan, X. Y., Wang, S. C., and He, L. C. (2011). Synthesis and cytotoxic evaluation of novel symmetrical taspine derivatives as anticancer agents. Med. Chem. 7 (4), 286–294. doi:10.2174/157340611796150914

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る