LRP-1 TRAFFICKING IS MODIFIED BY HEMIN IN ERYTHROLEUKEMIA CELLS

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

Mar del Plata, Provincia de Buenos Aires

Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015

SAIB

CB-P22LRP-1 TRAFFICKING IS MODIFIED BY HEMIN IN ERYTHROLEUKEMIA CELLSGrosso RA1; Sánchez MC2; Chiabrando GA2; Colombo MI1; Fader CM1.1Instituto de Histología y Embriología Dr Mario H Burgos, CCT, Mendoza. 2CIBICI-CONICET-UNC, Córdoba. E-mail: grossoruben88@gmail.comHemin is a natural compound which is necessary to form hemoglobin, the major blood protein. It is known that hemin induces erythroid cell differentiation but the molecular and cellular mechanisms involved in this process are still debated. 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 necessary for the final erythroid differentiation, leading to the degradation of non necessary organelles. Our objective was to elucidate the role of hemin-autophagy induction in LRP1 gene expression and trafficking. To determine these, we performed qRT-PCR in hemin-stimulated k562 cells. Interestingly, hemin caused an increased level of LRP1 and autophagic genes (i.e. MAP1a1b, Beclin1, Atg5). Moreover, to characterize the distribution of this receptor, different endosomal markers as Rab5, Rab7, LBPA and lysotrakcer were tested by inmunofluorescence. Confocal imaging has shown that LRP1 is mainly localized in autofagosomes (LC3 positive structures), late endosomes and lysosomal structures under hemin conditions. In general our results suggest that hemin induces autophagy, enhancing LRP1 and autophagic gene expression. Likewise, hemin would be targeting the LRP1 receptor to degradative compartiments, regulating its amount and activity.