Intracellular Ca2+ rhythmic activity in human glioblastoma multiforme cells
Resumen
El glioblastoma multiforme es un tumor cerebral letal. Los esfuerzos experimentales realizados hasta hoy han mejorado nuestra comprensión sobre la fisiopatología de dicho tumor. Sin embargo, es necesario encontrar objetivos moleculares para identificar vulnerabilidades potenciales y abordar su patogénesis eficientemente. Este trabajo estudió tumores cerebrales de glioblastoma multiforme extirpados de dos pacientes. A través de registros de Ca2+ intracelular in situ e in vitro, RT-PCR de punto final y experimentos histológicos se caracterizó parcialmente el origen de las respuestas de Ca2+ intracelular en células de glioblastoma multiforme humano expuestos a diversas concentraciones extracelulares iónicas y de transmisores químicos. Con ello se encontró que el 70% de las células de glioblastoma multiforme generaron movimientos espontáneos de Ca2+ intracelular, entre los cuales aproximadamente el 9% mostró fluctuaciones rítmicas, incluso en ausencia de calcio y sodio extracelular. Además, los antagonistas de IP3R y SERCA no inhibieron completamente las respuestas de Ca2+ intracelular, mientras que los estudios de RT-PCR mostraron la expresión de S100A9, KCNH1, SLC12A5 y SLC8A1. Estos resultados sugieren la participación de estas proteínas como parte de la maquinaria de señalización celular del glioblastoma multiforme.
Abstract
Glioblastoma multiforme is a lethal brain tumor. Experimental efforts to date have advanced our understanding of this tumor's pathophysiology. However, characterizing molecular targets is necessary to identify potential vulnerabilities and address its pathogenesis effectively. Here, we present excised glioblastoma multiforme brain tumors from two patients. We conducted in situ and in vitro Ca2+ imaging, end-point RT-PCR, and histological experiments to partially characterize the origin of intracellular Ca2+ responses in glioblastoma multiforme cells under diverse extracellular ionic and chemical-transmitter environments. These experimental approaches revealed that 70% of glioblastoma multiforme cells elicited spontaneous intracellular Ca2+ movements, among which 9% displayed rhythmic fluctuations, despite the absence of extracellular calcium and sodium. Moreover, IP3R and SERCA chemical antagonists were unable to completely inhibit these intracellular Ca2+ movements, while RT-PCR studies showed the expression of S100A9, KCNH1, SLC12A5, and SLC8A1. All these results suggest the participation of these proteins as part of the glioblastoma multiforme cell signaling machinery.
Keywords: human; cancer; neurotransmitter; glial cells; intracellular calcium.
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Referencias
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DOI: https://doi.org/10.25009/eb.v15i38.2632
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