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Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells.
Pelzl, Lisann; Hosseinzadeh, Zohreh; Al-Maghout, Tamer; Singh, Yogesh; Sahu, Itishri; Bissinger, Rosi; Schmidt, Sebastian; Alkahtani, Saad; Stournaras, Christos; Toulany, Mahmoud; Lang, Florian.
Afiliación
  • Pelzl L; Department of Internal Medicine III, Tuebingen, Germany.
  • Hosseinzadeh Z; Department of Internal Medicine III, Tuebingen, Germany.
  • Al-Maghout T; Experimental Retinal Prosthetics Group, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany.
  • Singh Y; Department of Internal Medicine III, Tuebingen, Germany.
  • Sahu I; Department of Internal Medicine III, Tuebingen, Germany.
  • Bissinger R; Department of Internal Medicine III, Tuebingen, Germany.
  • Schmidt S; Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad, India.
  • Alkahtani S; Department of Internal Medicine III, Tuebingen, Germany.
  • Stournaras C; Department of Internal Medicine III, Tuebingen, Germany.
  • Toulany M; Department of Biochemistry, University of Crete Medical School, Heraklion, Greece.
  • Lang F; Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia.
Cell Physiol Biochem ; 42(3): 1240-1251, 2017.
Article en En | MEDLINE | ID: mdl-28683437
BACKGROUND/AIMS: Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. METHODS: In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (Δ[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. RESULTS: The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of Δ[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 µM) significantly blunted Δ[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. CONCLUSIONS: Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Neoplasias Cerebelosas / Resistencia a Antineoplásicos / Intercambiador de Sodio-Calcio / Meduloblastoma Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Neoplasias Cerebelosas / Resistencia a Antineoplásicos / Intercambiador de Sodio-Calcio / Meduloblastoma Límite: Humans Idioma: En Revista: Cell Physiol Biochem Asunto de la revista: BIOQUIMICA / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania