Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release from the endoplasmic reticulum by AMP-activated kinase modulators.

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. Copyright © 2018 Elsevier Ltd. All rights reserved.

Citation

Jessica Arias-Del-Val, Jaime Santo-Domingo, Paloma García-Casas, Pilar Alvarez-Illera, Antonio Núñez Galindo, Andreas Wiederkehr, Rosalba I Fonteriz, Mayte Montero, Javier Alvarez. Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release from the endoplasmic reticulum by AMP-activated kinase modulators. Cell calcium. 2019 Jan;77:68-76

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PMID: 30557841

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