HEMIN INDUCES AUTOPHAGY IN A LEUKEMIC ERYTHROBLAST CELL LINE THROUGH THE LRP1 RECEPTOR

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

BIOSCIENCE REPORTS

PORTLAND PRESS LTD

Lugar: Londres; Año: 2019

0144-8463

Hemin is an erythropoietic inductor capable of inducing autophagy in erythroid-like cell lines. Low density lipoprotein receptor-related protein 1 (LRP1) is a transmembrane receptor involved in a wide range of cellular processes, such as proliferation, differentiation and metabolism. Our aim was to evaluate whether LRP1 is responsible for hemin activity in K562 cells, with the results demonstrating a 3-fold increase in LRP1 gene expression levels (p values < 0.001) when assessed by qRT-PCR. Moreover, a 70% higher protein amount was observed compared to control condition (p values < 0.01) by Western blot. Time kinetic assays demonstrated a peak in LC3II levels after 8 h of hemin stimulation and the localization of LRP1 in the autophagosome structures. Silencing LRP1 by siRNA decreased drastically the hemin-induced autophagy activity by almost 80% compared with control cells (p values < 0.01). Confocal localization and biochemical analysis indicated a significant redistribution of LRP1 from early endosomes and recycling compartments to late endosomes and autophagolysosomes, where the receptor is degraded. We conclude that LRP1 is responsible for hemin-induced autophagy activity in the erythroblastic cell line and that hemin-LRP1 complex activation promotes a self-regulation of the receptor. Our results suggest that hemin, via the LRP1 receptor, favors erythroid maturation by inducing an autophagic response, making it a possible therapeutic candidate to helps in the treatment of hematological disorders.