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A halocin acting on Na+/H+ exchanger of Haloarchaea as a new type of inhibitor in NHE of mammals

Una halocina que actúa sobre el intercambiador Na+/H+ de Haloarchaea como un nuevo tipo de inhibidor de NHE de mamíferos.

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Abstract

The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaeaHaloferax gibbonsii) to inhibit Na+/H+ exchange (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts).In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a, specific inhibitory activity in NHE of eukaryotic cells.

Resumen

En el presente trabajo se evalúa la capacidad de la halocina H6 (una proteína tipo bacteriocina producida por la haloarchaeaHaloferax gibbonsii) para inhibir el intercambiador Na+/H+ (NHE) de céludas de mamífero y su posible eficacia cardioprotectora frente a los daños causados por isquemia-reperfusión del miocardio. En experimentosin vitro H6 inhibe la actividad de NHE (determinada por citometría de flujo) de forma dosis-dependiente tanto en líneas celulares de mamíferos (HEK293, NIH3T3, Jurkat y HL-1) como en cultivos primarios de miocitos y fibroblastos aislados de músculo esquelético humano. En experimentosin vivo se utilizó un modelo de isquemia-reperfusión en perros por oclusión de la arteria coronaria (dos horas de isquemia y tres de reperfusión). En animales tratados con halocina H6 se produjo una disminución significativa a nivel estadístico, tanto del número de latidos ectópicos ventriculares como del tamaño del infarto, mientras que no se produjeron cambios tanto en la presión sanguínea como en el ritmo cardíaco. Hasta la fecha la halocina H6 es la única molécula biológica descrita que ejerce una actividad inhibidora específica sobre el NHE de células eucariotas.

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Authors and Affiliations

  1. Instituto de Biomedicina, Spanish Council for Scientific Research CISC, Valencia

    J. L. Lequerica & M. Dolz

  2. Center for Cytometry and Cytomics, Department of Biochemistry and Molecular Biology, University of Valencia, Spain

    J. E. O’Connor

  3. Department of Physiology, University of Valencia, Spain

    L. Such, A. Alberola & A. Moya

  4. Division of Microbiology, Univ. Miguel Hernández, Elche, Spain

    I. Meseguer, M. Torreblanca & F. Colom

  5. Bioengineering Institute, University Miguel Hernández, Alicante, Spain

    B. Soria

Authors
  1. J. L. Lequerica
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  2. J. E. O’Connor
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  3. L. Such
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  4. A. Alberola
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  5. I. Meseguer
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  6. M. Dolz
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  7. M. Torreblanca
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  8. A. Moya
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Correspondence to J. L. Lequerica.

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Lequerica, J.L., O’Connor, J.E., Such, L. et al. A halocin acting on Na+/H+ exchanger of Haloarchaea as a new type of inhibitor in NHE of mammals. J. Physiol. Biochem. 62, 253–262 (2006). https://doi.org/10.1007/BF03165754

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  • DOI: https://doi.org/10.1007/BF03165754

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