Reactive oxygen species participate in regulating intracellular signaling pathways. Herein, we investigated the reported opposite effects of hydrogen peroxide (H2O2) on metabolic signaling mediated by activated α1- and β-adrenoceptors (ARs) in hepatocytes. In isolated rat hepatocytes, stimulation of α1-AR increases H2O2 production via NADPH oxidase 2 (NOX2) activation. We find that the H2O2 thus produced is essential for α1-AR-mediated activation of the classical hepatic glycogenolytic, gluconeogenic, and ureagenic responses. However, H2O2 inhibits β-AR-mediated activation of these metabolic responses. We show that H2O2 mediates its effects on α1-AR and β-AR by permeating cells through aquaporin 8 (AQP8) channels and promoting Ca2+ mobilization. Thus, our findings reveal a novel NOX2-H2O2-AQP8-Ca2+ signaling cascade acting downstream of α1-AR in hepatocytes, which, by negatively regulating β-AR signaling, establishes negative crosstalk between the two pathways.
CITATION STYLE
Vilchis-Landeros, M., Guinzberg, R., Riveros-Rosas, H., Villalobos-Molina, R., & Piña, E. (2020). Aquaporin 8 is involved in H2O2-mediated differential regulation of metabolic signaling by α1- and β-adrenoceptors in hepatocytes. FEBS Letters, 594(10), 1564–1576. https://doi.org/10.1002/1873-3468.13763
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