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

Ruben Adrian Grosso, Paula Virginia Subirada Caldarone, María Cecilia Sánchez, Gustavo Alberto Chiabrando, Maŕia Isabel Colombo, Claudio Marcelo Fader*


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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 (P-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 (P-values <0.01) byWestern 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 (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 help in the treatment of hematological disorders.

TidsskriftBioscience Reports
Udgave nummer1
Antal sider17
StatusUdgivet - 3. jan. 2019
Udgivet eksterntJa

Bibliografisk note

Funding Information:
This work was partly supported by the Agencia Nacional de Promoción Científica y Tecnológica [grant number PICT 2013-2335]; and the Universidad Nacional de Cuyo [grant number SeCTyP K013 (to C.M.F.)].


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