RT info:eu-repo/semantics/article
T1 Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release from the endoplasmic reticulum by AMP-activated kinase modulators
A1 Arias del Val, Jessica
A1 Santo Domingo Mayoral, Jaime
A1 García Casas, Paloma
A1 Álvarez Illera, María Pilar
A1 Núñez Galindo, Antonio
A1 Wiederkehr, Andreas
A1 Fonteriz García, Rosalba Inés
A1 Montero Zoccola, María Teresa
A1 Álvarez Martín, Javier
K1 AMPK, Inositol-1,4,5-trisphosphate receptor, Ca2+ signaling, Endoplasmic reticulum, A769662, Dorsomorphin
AB The 5' AMP-activated protein kinase (AMPK) is a nutrient-sensitive kinase that plays a key role in the control of cellular energy metabolism. We have explored here the relationship between AMPK and Ca2+ signaling by looking at the effect of an AMPK activator (A769662) and an AMPK inhibitor (dorsomorphin) on histamine induced Ca2+-release from the endoplasmic reticulum (ER) in HeLa cells. Our data show that incubation with A769662 (EC50=29 μM) inhibited histamine-induced Ca2+-release from the ER in intact cells, as well as inositol-1,4,5-trisphosphate (IP3)-induced Ca2+ release in permeabilized cells. On the contrary, dorsomorphin (EC50=0.4 μM) activated both histamine and IP3-induced Ca2+-release and reversed the effect of A769662. These results suggest a direct effect of AMPK regulation on IP3 receptor (IP3R) function. A phosphoproteomic study did not reveal changes in IP3R phosphorylation, but showed significant changes in phosphorylation of proteins placed upstream in the IP3R interactome and in several proteins related with Ca2+ metabolism, which could be candidates to mediate the effects observed. In conclusion, our data suggest that AMPK negatively regulates IP3R. This effect constitutes a novel and very important link between Ca2+ signaling and the AMPK pathway.
PB Elsevier
SN 0143-4160
YR 2019
FD 2019
LK https://uvadoc.uva.es/handle/10324/66247
UL https://uvadoc.uva.es/handle/10324/66247
LA eng
NO Cell Calcium, Enero 2019, 77, 68-76
NO Producción Científica
DS UVaDOC
RD 22-nov-2024