RT Dissertation/Thesis
T1 Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
A1 García Rúa, Vanessa
A2 Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía.Facultade de Bioloxía. Departamento de Medicina. Laboratorio de Investigación en Cardioloxía Celular e Molecular do Instituto de Investigacións Sanitarias, 
K1 síndrome metabólico
K1 receptores endolisosomales
K1 TPCS
K1 sistema cardiovascular
AB Rationale: Autophagy participates in both physiological and pathologicalremodeling of the heart. The endolysosomal two-pore channels TPC1 and TPC2 havebeen implicated in the regulation of metabolism and autophagy. Objective: To study therole of TPC1 and TPC2 in cardiac metabolism and in basal and induced cardiacautophagic activity. Methods and Results: The cardiac tissue of TPC1 knockout miceshowed significative alterations in key proteins related with cardiac metabolism as wellas with cardiac contraction and/or structure maintenance. siRNA depletion of TPC1induced an increase in glucose uptake and on GLUT-4 translocation in culturedcardiomyocytes. In addition, starvation induced a significant increase in TPC1 andTPC2 transcripts and protein levels that paralleled the increase in autophagic flux(identified by increased LC3-II and decreased p62 levels) in cultured cardiomyocytes.SiRNA depletion of TPC2 alone or together with TPC1 increased both LC3-II and p62levels under basal conditions and in response to starvation, suggesting a change in theautophagic process. Electron micrographs of cardiac tissue from TPC1/2 doubleknockout mice showed that cardiomyocytes contained large numbers of immaturelysosomes with diameters significantly smaller than those of wild-type mice. In cardiactissues from both humans and rats, TPC1 and TPC2 transcripts and protein levels werehigher in females than in males and increased in heart failure patients compared tohealthy controls. Conclusions: These data are the first evidence showing that the TPCsand the endolysosomal system could be involved in cardiac metabolism, cardiacautophagy, and thus, in the physiopathology of cardiovascular diseases.
YR 2016
FD 2016-02-16
LK http://hdl.handle.net/10347/13847
UL http://hdl.handle.net/10347/13847
LA spa
DS Minerva
RD 28 abr 2026