Maintenance of red blood cell integrity by AMP-activated protein kinase alpha1 catalytic subunit.
AMP-activated protein kinase (AMPK) plays a pivotal role in regulating cellular energy metabolism. We previously showed that AMPKalpha1-/- mice develop moderate anemia associated with splenomegaly and high reticulocytosis. Here, we report that splenectomy of AMPKalpha1-/- mice worsened anemia supporting evidence that AMPKalpha1-/- mice developed a compensatory response through extramedullary erythropoiesis in the spleen. Transplantation of bone marrow from AMPKalpha1-/- mice into wild-type recipients recapitulated the hematologic phenotype. Further, AMPKalpha1-/- red blood cells (RBC) showed less deformability in response to shear stress limiting their membrane flexibility. Thus, our results highlight the crucial role of AMPK to preserve RBC integrity.
Foretz
Marc
M
Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique (UMR8104), Paris, France; INSERM, U1016, Paris, France.
Guihard
Soizic
S
Leclerc
Jocelyne
J
Fauveau
Véronique
V
Couty
Jean-Pierre
JP
Andris
Fabienne
F
Gaudry
Murielle
M
Andreelli
Fabrizio
F
Vaulont
Sophie
S
Viollet
Benoit
B
D055372:AMP-Activated Protein Kinases / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D000740:Anemia / Q000097:blood / Q000201:enzymology / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D004907:Erythrocyte Deformability / Q000235:genetics / Q000502:physiology*; D004920:Erythropoiesis; D006411:Hematopoiesis, Extramedullary; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009996:Osmotic Fragility; D013156:Splenectomy; D013163:Splenomegaly / Q000097:blood / Q000201:enzymology / Q000235:genetics
C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases