RT Journal Article
T1 Dipyridamole activates adenosine A2B receptor and AMPK/cAMP signaling and promotes myogenic differentiation of myoblastic C2C12 cells
A1 Marco Bonilla, Miguel
A1 Herencia, Raquel
A1 Fresnadillo, María
A1 Huete Toral, Fernando
A1 Carracedo Rodríguez, Juan Gonzalo
A1 Largo, Raquel
A1 Herrero Beaumont, Gabriel
A1 Mediero, Aranzazú
AB Introduction: Sarcopenia is defined as a loss of muscle mass and strength. ATP homeostasis is crucial during myogenesis. We determined how the purinergic system modulates myogenesis using dipyridamole (blocks adenosine taken up by the cells) and tenofovir (inhibits ATP release) in a myoblast cell line. Methods: C2C12 cells were differentiated in the presence/absence of tenofovir/dipyridamole, with/without the A2B selective inhibitor PSB-603. Extra-/intracellular nucleotides were examined via HPLC. The expression of muscle differentiation proteins (Pax7, Mif5, MyoD, MyoG, and MHC), PKA/CREB, adenosine receptors (A1, A2A, A2B, and A3), ATP-channel pannexin-1 and the P2X7 receptor was analyzed via WB and RT-PCR. cAMP and AMPK activation was measured. Results: Tenofovir increased intracellular ATP and reduced extracellular adenosine, decreasing Pax7 expression and increasing MHC expression prematurely. Dipyridamole increased intracellular AMP and extracellular adenosine, counteracting the premature myogenesis promoted by tenofovir. All adenosine receptors were expressed during differentiation with dipyridamole, increasing A2B expression. Tenofovir maintained inactive AMPK and decreased cAMP levels, as well as PKAα and pCREB expression, which were recovered with dipyridamole. Discussion: Adenosine and ATP act as mediators in muscle myogenesis. The blockade of ATP release by tenofovir promotes premature myogenesis, with dipyridamole counteracting the premature differentiation promoted by tenofovir via the adenosine A2B receptor and cAMP/AMPK pathways. Therefore, dipyridamole might be of interest as a therapeutic approach in sarcopenia. Copyright © 2023 Marco-Bonilla, Herencia, Fresnadillo, Huete-Toral, Carracedo, Largo, Herrero-Beaumont and Mediero.
PB Frontiers Media
YR 2023
FD 2023-09-12
LK https://hdl.handle.net/20.500.14352/88628
UL https://hdl.handle.net/20.500.14352/88628
LA eng
NO Marco-Bonilla M, Herencia R, Fresnadillo M, Huete-Toral F, Carracedo G, Largo R, Herrero-Beaumont G and Mediero A (2023) Dipyridamole activates adenosine A2B receptor and AMPK/cAMP signaling and promotes myogenic differentiation of myoblastic C2C12 cells. Front. Pharmacol. 14:1247664. doi: 10.3389/fphar.2023.1247664
NO Instituto de Salud Carlos III (España)
NO Fondo Europeo de Desarrollo Regional (FEDER)
DS Docta Complutense
RD 17 abr 2025