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    Por favor, use este identificador para citar o enlazar este ítem:http://uvadoc.uva.es/handle/10324/35192

    Título
    Caffeine chelates calcium in the lumen of the endoplasmic reticulum
    Autor
    Rojo Ruiz, JonatanAutoridad UVA Orcid
    Rodríguez Prados, Macarena
    Río Lorenzo, Alba delAutoridad UVA Orcid
    Alonso Alonso, María TeresaAutoridad UVA
    García-Sancho Martín, Francisco JavierAutoridad UVA Orcid
    Año del Documento
    2018
    Editorial
    Portland Press
    Descripción
    Producción Científica
    Documento Fuente
    Biochemical Journal, 2018, 475 (22) 3639-3649
    Resumo
    Cytosolic Ca2+ signals are often amplified by massive calcium release from the endoplasmic reticulum (ER). This calcium-induced calcium release (CICR) occurs by activation of an ER Ca2+ channel, the ryanodine receptor (RyR), which is facilitated by both cytosolic- and ER Ca2+ levels. Caffeine sensitizes RyR to Ca2+ and promotes ER Ca2+ release at basal cytosolic Ca2+ levels. This outcome is frequently used as a readout for the presence of CICR. By monitoring ER luminal Ca2+ with the low-affinity genetic Ca2+ probe erGAP3, we find here that application of 50 mM caffeine rapidly reduces the Ca2+ content of the ER in HeLa cells by ∼50%. Interestingly, this apparent ER Ca2+ release does not go along with the expected cytosolic Ca2+ increase. These results can be explained by Ca2+ chelation by caffeine inside the ER. Ca2+-overloaded mitochondria also display a drop of the matrix Ca2+ concentration upon caffeine addition. In contrast, in the cytosol, with a low free Ca2+ concentration (10−7 M), no chelation is observed. Expression of RyR3 sensitizes the responses to caffeine with effects both in the ER (increase in Ca2+ release) and in the cytosol (increase in Ca2+ peak) at low caffeine concentrations (0.3–1 mM) that have no effects in control cells. Our results illustrate the fact that simultaneous monitoring of both cytosolic- and ER Ca2+ are necessary to understand the action of caffeine and raise concerns against the use of high concentrations of caffeine as a readout of the presence of CICR.
    Palabras Clave
    Calcio
    Calcium
    ISSN
    0264-6021
    Revisión por pares
    SI
    DOI
    10.1042/BCJ20180532
    Patrocinador
    Ministerio de Economía, Industria y Competitividad (Project BFU2017-83066-P)
    Version del Editor
    http://www.biochemj.org/content/475/22/3639
    Idioma
    eng
    URI
    http://uvadoc.uva.es/handle/10324/35192
    Derechos
    openAccess
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    • IBGM - Artículos de revista [79]
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    Universidad de Valladolid

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