Hemin induces autophagy in a leukemic erythroblast cell line through the LRP1 receptor

• Published in: Bioscience reports Vol. 39; no. 1
• Main Authors: Grosso, Ruben Adrian, Caldarone, Paula Virginia Subirada, Sánchez, María Cecilia, Chiabrando, Gustavo Alberto, Colombo, María Isabel, Fader, Claudio Marcelo
• Format: Journal Article
• Language: English
• Published: England Portland Press Ltd 31.01.2019
• Subjects: Autophagosomes - drug effects; Autophagosomes - metabolism; Autophagy - drug effects; Autophagy - genetics; Gene Expression Regulation, Leukemic; HeLa Cells; Hemin - pharmacology; Humans; K562 Cells; Low Density Lipoprotein Receptor-Related Protein-1 - antagonists & inhibitors; Low Density Lipoprotein Receptor-Related Protein-1 - genetics; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Protein Transport - drug effects; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Signal Transduction; cell differentiation; autophagy; LRP1; trafficking
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/bsr20181156

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 three-fold increase in LRP1 gene expression levels ( -values <0.001) when assessed by quantitative real-time RT-PCR (qRT-PCR). Moreover, a 70% higher protein amount was observed compared with control condition ( -values <0.01) by Western blot (WB). Time kinetic assays demonstrated a peak in light chain 3 (LC3) II (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 ( -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 help in the treatment of hematological disorders.