LRP1 PARTICIPATES IN HEMIN-INDUCED AUTOPHAGY, MODYFING ITS TRAFFICKING IN ERYTHROLEUKEMIA CELLS

GROSSO RA; CHIABRANDO GA; SÁNCHEZ MC; FADER CM; MARTÍN JM; COLOMBO MI

Cordoba

Congreso; 52th reunión anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

SAIB

Hemin is a natural compound which stimulates hemoglobin synthesis and organelle clearance necessary in erythropoiesis. The transmembrane low density lipoprotein receptor related protein 1 (LRP1), is the scavenger for the hemin-hemopexine complex that allows its internalization. Autophagy is a lysosomal-degradative process leading to degradation of non-necessary organelles. Our aim is to elucidate the possible role of LRP1 in the hemin-induced autophagy. Our preliminary results have shown that Hemin or resveratrol (autophagy inductors) are able to induce LRP1 gene expression and increase the protein levels. Moreover, in hemin-stimulated K562 cells (erythroleukemia cells line), it was observed an increased colocalization of LRP1 structures with late endosomes, lysosomes and also with autophagosomes. This is a new finding in LRP1 trafficking being reported that the receptor is only associated with early endosomes. Interestingly, silencing of LRP1, hamper the hemin-stimulated autophagy in K562 and HeLa cells. Moreover, in cells incubated in presence of hemin, an additional band of was detected by Western blot in a time-dependent manner. The study of the molecular mechanisms that regulate the autophagy induction could provide important data to understand more deeply the mechanisms of proliferation and differentiation of red line cells, especially in hematologic diseases such as leukemia.