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Regulation of hypoxia response by NO in pluripotent stem cells

AutorCaballano-Infantes, Estefanía; Hitos, Ana B. ; Díaz, Irene ; Cahuana, Gladys M. ; Hmadcha, Abdelkrim ; Martín, Franz ; Soria Escoms, Bernat ; Tejedo Huamán, Juan Rigoberto ; Bedoya Bergua, Francisco Javier
Fecha de publicación2014
EditorSociedad Española de Bioquímica y Biología Molecular
CitaciónXXXVII Congreso SEBBM (2014)
ResumenThe expansion of pluripotent cells (ESCs and iPSCs) under conditions that maintain their pluripotency is necessary to implement a cell therapy program. Previously, we have described that low nitric oxide donor diethylenetriamine/nitric oxide adduct (DETA-NO) added to the culture medium, promote the expansion of these cell types. The mechanisms involved in this response are not yet known. We present evidences that when ESC and iPSCs are grown under normoxia in presence of Nitric Oxide (NO) triggers a similarresponse to hypoxia, thus maintaining the pluripotency. We have studied the stability of protein HIF-1α (Hypoxia Inducible Factor) in presence of low NO. Because of the close relationship between hypoxia, metabolism, mitochondrial function and pluripotency we have analyzed by qRT-PCR the expression of genes involved in glucose metabolism and the glycolytic pathway such as: HK2, LDHA and PDK1; besides other gene targets of HIF. We further analyzed the expression of genes involved in mitochondrial biogenesis such as PGC1α, TFAM and NRF1 and we have observed that low NO maintains the same expression that in hypoxia. The study of the mitochondrial membrane potential using MitoTracker dye, showed a slight decrease in the membrane potential in cells with NO in normoxia, this indicated that NO might decrease the mitochondrial function. We will analyze other metabolic parameters, to determinate if this molecule regulates mitochondrial function and mimics Hypoxia Response. The knowledge of the role of NO in the Response to Hypoxia and the mechanisms that help to maintain self renewal in pluripotent cells grown under normoxia, can help to the design of culture media where NO could be optimal for stem cell expansion in the performance of future cell therapies.
DescripciónResumen del póster presentado al XXXVII Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Granada del 9 al 12 de septiembre de 2014.
URIhttp://hdl.handle.net/10261/165889
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