CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
AGGREGATED LDL AFFECTS THE REGULATORY ACTION OF LRP1 ON THE INSULIN-DEPENDENT INTRACELLULAR SIGNALING AND GLUT4 TRAFFICKING IN HL-1 CARDIOMYOCYTES
Autor/es:
LLORENTE-CORTES VICENTA; NAZARRE LAURA; VAZQUEZ, MAXIMILIANO; BENITEZ ALEYDA; CHIABRANDO, GUSTAVO; GUTIERREZ VICTORIA; ACTIS DATO, VIRGINA
Lugar:
Buenos Aires
Reunión:
Congreso; I Reunión Conjunta de Sociedades de Biociencias; 2017
Institución organizadora:
SAIB, SAIC, SAI, SAA, SAB, SAFE, SAFIS, SAH, SAP
Resumen:
Diabetes mellitus (DM) is a metabolic disorder mainly characterized by hyperglycemia, dyslipidemia and hyperinsulinemia, and cardiovascular disease (CVD) is the main complication of DM. DM patients usually have increased levels of atherogenic subfractions of low-density lipoproteins (LDL), such as aggregated LDL (agLDL). This latter lipoprotein is responsible to induce anomalous intracellular lipid accumulation in cardiomyocytes in a low-density lipoprotein receptor-related protein-1 (LRP1)-dependent manner. LRP1 is an endocytic and signaling receptor, belonging to the LDL receptor family. Moreover, LRP1 regulates the intracellular trafficking of membrane proteins and vesicles, including insulin receptor (IR), GLUT4 and GSVs (GLUT4 storage vesicles). Thus, it has been suggested that a functional deficiency of LRP1 would be directly associated with insulin resistance disorders. In the present work, we evaluate whether agLDL via its interaction with LRP1 may affect the insulin-induced intracellular signaling and GLUT4 trafficking to the plasma membrane (PM) in HL-1 cardiomyocytes. By quantitative PCR and Western blot analysis we determined that LRP1 and GLUT4 expression were unaffected after agLDL treatment for 8 h at 37 °C. By confocal microscopy we found a substantial modification of the intracellular localization of LRP1 and GLUT4 in agLDL-stimulated cells. Also, after insulin stimulus (100 nM) in agLDL-preincubated cells, a decreased level of Akt and AS160 phosphorylation was observed compared to unpreincubated cells. By immunoprecipitation we found that agLDL-preincubated cells showed a weakly molecular association between IR and LRP1 with respect to control conditions. Finally, by biotin-labeling protein assay we demonstrated that agLDL reduced the GLUT4 translocation to the plasma membrane in insulin-stimulated cells. Thus, we conclude that LRP1 is a key regulator of insulin response and glucose metabolism in cardiomyocytes, being its action affected by agLDL.