@article{Meriem Ladli_Cyrielle Richard_Lilia Cantero Aguilar_Sarah Ducamp_Sabrina Bondu_Pierre Sujobert_Jérôme Tamburini_Catherine Lacombe_Nabih Azar_Marc Foretz_Yael Zermati_Patrick Mayeux_Benoit Viollet_Frédérique Verdier_2019, place={Pavia, Italy}, title={Finely-tuned regulation of AMP-activated protein kinase is crucial for human adult erythropoiesis}, volume={104}, url={https://haematologica.org/article/view/8893}, DOI={10.3324/haematol.2018.191403}, abstractNote={AMP-activated protein kinase (AMPK) is a heterotrimeric complex containing α, β, and γ subunits involved in maintaining integrity and survival of murine red blood cells. Indeed, <em>Ampk</em> α<em>1<sup>−/−</sup></em>, <em>Ampk β1<sup>−/−</sup></em> and <em>Ampk γ1<sup>−/−</sup></em> mice develop hemolytic anemia and the plasma membrane of their red blood cells shows elasticity defects. The membrane composition evolves continuously along erythropoiesis and during red blood cell maturation; defects due to the absence of Ampk could be initiated during erythropoiesis. We, therefore, studied the role of AMPK during human erythropoiesis. Our data show that AMPK activation had two distinct phases in primary erythroblasts. The phosphorylation of AMPK (Thr172) and its target acetyl CoA carboxylase (Ser79) was elevated in immature erythroblasts (glycophorin A<sup>low</sup>), then decreased conjointly with erythroid differentiation. In erythroblasts, knockdown of the α1 catalytic subunit by short hairpin RNA led to a decrease in cell proliferation and alterations in the expression of membrane proteins (band 3 and glycophorin A) associated with an increase in phosphorylation of adducin (Ser726). AMPK activation in mature erythroblasts (glycophorin A<sup>high</sup&gt;), achieved through the use of direct activators (GSK621 and compound 991), induced cell cycle arrest in the S phase, the induction of autophagy and caspase-dependent apoptosis, whereas no such effects were observed in similarly treated immature erythroblasts. Thus, our work suggests that AMPK activation during the final stages of erythropoiesis is deleterious. As the use of direct AMPK activators is being considered as a treatment in several pathologies (diabetes, acute myeloid leukemia), this observation is pivotal. Our data highlighted the importance of the finely-tuned regulation of AMPK during human erythropoiesis.}, number={5}, journal={Haematologica}, author={Meriem Ladli and Cyrielle Richard and Lilia Cantero Aguilar and Sarah Ducamp and Sabrina Bondu and Pierre Sujobert and Jérôme Tamburini and Catherine Lacombe and Nabih Azar and Marc Foretz and Yael Zermati and Patrick Mayeux and Benoit Viollet and Frédérique Verdier}, year={2019}, month={Apr.}, pages={907-918} }