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Research ArticleArticle

Vm24, a Natural Immunosuppressive Peptide, Potently and Selectively Blocks Kv1.3 Potassium Channels of Human T Cells

Zoltan Varga, 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 and Gyorgy Panyi
Molecular Pharmacology September 2012, 82 (3) 372-382; DOI: https://doi.org/10.1124/mol.112.078006
Zoltan Varga
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Georgina Gurrola-Briones
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Ferenc Papp
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Ricardo C. Rodríguez de la Vega
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Gustavo Pedraza-Alva
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Rajeev B. Tajhya
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Rezso Gaspar
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Luis Cardenas
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Yvonne Rosenstein
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Christine Beeton
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Lourival D. Possani
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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Gyorgy Panyi
Department of Biophysics and Cell Biology, Research Center for Molecular Medicine, University of Debrecen, Debrecen, Hungary (Z.V., F.P., R.G., G.P.); Departments of Molecular Medicine and Bioprocesses (G.G.-B., G.P.-A., Y.R., L.D.P.) and Molecular and Plant Biology (L.C.), Institute of Biotechnology, National Autonomous University of Mexico, Cuernavaca, Mexico; Ecology, Systematics, and Evolution Laboratory, University of Paris-South, Orsay, France (R.C.R.V.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas (R.B.T., C.B.)
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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 (Kd = 2.9 pM) and exhibits >1500-fold selectivity over other ion channels assayed. It inhibits the proliferation and Ca2+ 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.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS073712]; the Hungarian Scientific Research Fund [Grants K 60740, NK 61412]; the Hungarian Social Renewal Operational Program [Grants TÁMOP-4.2.2-08/1/2008-0019, TÁMOP-4.2.1/B-09/1/KONV-2010-007, TÁMOP-4.2.2-A-11/1/KONV-2012-0025], General Management of Academic Personnel Matters, National Autonomous University of Mexico [Grant IN204110]; the National Council for Science and Technology of Mexico; the Hungarian Science and Technology Foundation [Grant MX-10/207], and the European Union Seventh Framework Program [Grant 246556] (to R.C.R.V.). Z.V. is a Bolyai Fellow.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    http://dx.doi.org/10.1124/mol.112.078006.

  • ABBREVIATIONS:

    TEM
    effector memory T
    [Ca2+]i
    cytosolic free Ca2+ concentration
    CFSE
    carboxyfluorescein succinimidyl ester
    FACS
    fluorescence-activated cell sorting
    RCF
    remaining current fraction
    GFP
    green fluorescent protein
    DTH
    delayed-type hypersensitivity
    PBS
    phosphate-buffered saline
    ShK
    Stichodactyla helianthus toxin
    OSK1
    Orthochirus scrobiculosus toxin 1
    BmKTx
    potassium blocking toxin from Buthus martensi
    HgTx1
    hongotoxin1
    MgTx
    margatoxin
    HsTx1
    Heterometrus spinifer toxin
    ChTx
    charybdotoxin
    mAb
    monoclonal antibody
    h
    human
    m
    mouse
    r
    rat.

  • Received January 31, 2012.
  • Accepted May 23, 2012.
  • Copyright © 2012 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 82 (3)
Molecular Pharmacology
Vol. 82, Issue 3
1 Sep 2012
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Research ArticleArticle

Immunosuppressive Peptide Toxin from Scorpion Venom

Zoltan Varga, 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 and Gyorgy Panyi
Molecular Pharmacology September 1, 2012, 82 (3) 372-382; DOI: https://doi.org/10.1124/mol.112.078006

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Research ArticleArticle

Immunosuppressive Peptide Toxin from Scorpion Venom

Zoltan Varga, 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 and Gyorgy Panyi
Molecular Pharmacology September 1, 2012, 82 (3) 372-382; DOI: https://doi.org/10.1124/mol.112.078006
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