Literature DB >> 22622363

Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells.

Zoltan Varga1, Georgina Gurrola-Briones, Ferenc Papp, Ricardo C Rodríguez de la Vega, Gustavo Pedraza-Alva, Rajeev B Tajhya, Rezso Gaspar, Luis Cardenas, Yvonne Rosenstein, Christine Beeton, Lourival D Possani, Gyorgy Panyi.   

Abstract

Blockade of Kv1.3 K(+) channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. Vm24 (α-KTx 23.1) is a novel 36-residue Kv1.3-specific peptide isolated from the venom of the scorpion Vaejovis mexicanus smithi. Vm24 inhibits Kv1.3 channels of human lymphocytes with high affinity (K(d) = 2.9 pM) and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits the proliferation and Ca(2+) signaling of human T cells in vitro and reduces delayed-type hypersensitivity reactions in rats in vivo. Our results indicate that Vm24 has exceptional pharmacological properties that make it an excellent candidate for treatment of certain autoimmune diseases.

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Year:  2012        PMID: 22622363      PMCID: PMC3422703          DOI: 10.1124/mol.112.078006

Source DB:  PubMed          Journal:  Mol Pharmacol        ISSN: 0026-895X            Impact factor:   4.436


  43 in total

Review 1.  K+ channel blockers: novel tools to inhibit T cell activation leading to specific immunosuppression.

Authors:  G Panyi; L D Possani; R C Rodríguez de la Vega; R Gáspár; Z Varga
Journal:  Curr Pharm Des       Date:  2006       Impact factor: 3.116

2.  TCR-dependent cell response is modulated by the timing of CD43 engagement.

Authors:  Nora A Fierro; Gustavo Pedraza-Alva; Yvonne Rosenstein
Journal:  J Immunol       Date:  2006-06-15       Impact factor: 5.422

3.  Induction and monitoring of active delayed type hypersensitivity (DTH) in rats.

Authors:  Christine Beeton; K George Chandy
Journal:  J Vis Exp       Date:  2007-07-19       Impact factor: 1.355

4.  Proteomic analysis of the venom from the scorpion Tityus stigmurus: biochemical and physiological comparison with other Tityus species.

Authors:  C V F Batista; S A Román-González; S P Salas-Castillo; F Z Zamudio; F Gómez-Lagunas; L D Possani
Journal:  Comp Biochem Physiol C Toxicol Pharmacol       Date:  2006-12-16       Impact factor: 3.228

5.  A selective blocker of Kv1.2 and Kv1.3 potassium channels from the venom of the scorpion Centruroides suffusus suffusus.

Authors:  Gerardo Corzo; Ferenc Papp; Zoltan Varga; Omar Barraza; Pavel G Espino-Solis; Ricardo C Rodríguez de la Vega; Rezso Gaspar; Gyorgy Panyi; Lourival D Possani
Journal:  Biochem Pharmacol       Date:  2008-08-22       Impact factor: 5.858

6.  High-throughput profiling of ion channel activity in primary human lymphocytes.

Authors:  Daniel J Estes; Sohiel Memarsadeghi; Steven K Lundy; Francesc Marti; Daniel D Mikol; David A Fox; Michael Mayer
Journal:  Anal Chem       Date:  2008-04-24       Impact factor: 6.986

7.  TWIK-related acid-sensitive K+ channel 1 (TASK1) and TASK3 critically influence T lymphocyte effector functions.

Authors:  Sven G Meuth; Stefan Bittner; Patrick Meuth; Ole J Simon; Thomas Budde; Heinz Wiendl
Journal:  J Biol Chem       Date:  2008-03-28       Impact factor: 5.157

8.  Characterization of the functional properties of the voltage-gated potassium channel Kv1.3 in human CD4+ T lymphocytes.

Authors:  Lina Hu; Michael Pennington; Qiong Jiang; Katharine A Whartenby; Peter A Calabresi
Journal:  J Immunol       Date:  2007-10-01       Impact factor: 5.422

9.  Structural basis of a potent peptide inhibitor designed for Kv1.3 channel, a therapeutic target of autoimmune disease.

Authors:  Song Han; Hong Yi; Shi-Jin Yin; Zong-Yun Chen; Hui Liu; Zhi-Jian Cao; Ying-Liang Wu; Wen-Xin Li
Journal:  J Biol Chem       Date:  2008-05-14       Impact factor: 5.157

10.  Measurement of proliferative responses of cultured lymphocytes.

Authors:  Linda Mesler Muul; Christopher Silvin; Stephen P James; Fabio Candotti
Journal:  Curr Protoc Immunol       Date:  2008-08
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  34 in total

1.  Recombinant expression of Intrepicalcin from the scorpion Vaejovis intrepidus and its effect on skeletal ryanodine receptors.

Authors:  Leonel Vargas-Jaimes; Liang Xiao; Jing Zhang; Lourival D Possani; Héctor H Valdivia; Verónica Quintero-Hernández
Journal:  Biochim Biophys Acta Gen Subj       Date:  2017-01-31       Impact factor: 3.770

2.  Rational design of a Kv1.3 channel-blocking antibody as a selective immunosuppressant.

Authors:  Rongsheng E Wang; Ying Wang; Yuhan Zhang; Chase Gabrelow; Yong Zhang; Victor Chi; Qiangwei Fu; Xiaozhou Luo; Danling Wang; Sean Joseph; Kristen Johnson; Arnab K Chatterjee; Timothy M Wright; Vân T B Nguyen-Tran; John Teijaro; Argyrios N Theofilopoulos; Peter G Schultz; Feng Wang
Journal:  Proc Natl Acad Sci U S A       Date:  2016-09-23       Impact factor: 11.205

3.  N-Terminally extended analogues of the K⁺ channel toxin from Stichodactyla helianthus as potent and selective blockers of the voltage-gated potassium channel Kv1.3.

Authors:  Shih C Chang; Redwan Huq; Sandeep Chhabra; Christine Beeton; Michael W Pennington; Brian J Smith; Raymond S Norton
Journal:  FEBS J       Date:  2015-04-23       Impact factor: 5.542

4.  Functionalized liposomes loaded with siRNAs targeting ion channels in effector memory T cells as a potential therapy for autoimmunity.

Authors:  Péter Hajdu; Ameet A Chimote; Tyler H Thompson; Youngmi Koo; Yeoheung Yun; Laura Conforti
Journal:  Biomaterials       Date:  2013-09-27       Impact factor: 12.479

5.  Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1: AN INTEGRATED TRANSCRIPTOMIC AND PROTEOMIC STUDY.

Authors:  Alexey I Kuzmenkov; Alexander A Vassilevski; Kseniya S Kudryashova; Oksana V Nekrasova; Steve Peigneur; Jan Tytgat; Alexey V Feofanov; Mikhail P Kirpichnikov; Eugene V Grishin
Journal:  J Biol Chem       Date:  2015-03-19       Impact factor: 5.157

6.  Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog.

Authors:  Mark R Tanner; Rajeev B Tajhya; Redwan Huq; Elizabeth J Gehrmann; Kathia E Rodarte; Mustafa A Atik; Raymond S Norton; Michael W Pennington; Christine Beeton
Journal:  Clin Immunol       Date:  2017-04-04       Impact factor: 3.969

7.  Role of the K(Ca)3.1 K+ channel in auricular lymph node CD4+ T-lymphocyte function of the delayed-type hypersensitivity model.

Authors:  Susumu Ohya; Erina Nakamura; Sayuri Horiba; Hiroaki Kito; Miki Matsui; Hisao Yamamura; Yuji Imaizumi
Journal:  Br J Pharmacol       Date:  2013-07       Impact factor: 8.739

Review 8.  Ion channels and anti-cancer immunity.

Authors:  Gyorgy Panyi; Christine Beeton; Antonio Felipe
Journal:  Philos Trans R Soc Lond B Biol Sci       Date:  2014-02-03       Impact factor: 6.237

9.  7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome.

Authors:  András Balajthy; Sándor Somodi; Zoltán Pethő; Mária Péter; Zoltán Varga; Gabriella P Szabó; György Paragh; László Vígh; György Panyi; Péter Hajdu
Journal:  Pflugers Arch       Date:  2016-06-17       Impact factor: 3.657

Review 10.  Review on Biological Characteristics of Kv1.3 and Its Role in Liver Diseases.

Authors:  Junda Liu; Xiong-Wen Lv; Lei Zhang; Hua Wang; Jun Li; Baoming Wu
Journal:  Front Pharmacol       Date:  2021-05-21       Impact factor: 5.810

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