Aquaporin 8 is involved in H 2 O 2 -mediated differential regulation of metabolic signaling by α 1 - and β-adrenoceptors in hepatocytes

FEBS Letters

article

Magdalena Vilchis-Landeros¹  Raquel Guinzberg¹  Héctor Riveros-Rosas¹  Rafael Villalobos-Molina²  Enrique Piña² 

[1] Universidad Nacional Autónoma de México;Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México;Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de Méxic

关键词: b-adrenergic receptors;    adrenaline;    Ca2+ mobilization;    epinephrine;    gluconeogenesis;    glycogenolysis;    H2O2;    hepatocytes;    signaling;    ureagenesis;    a1-adrenergic receptors;   

DOI  :  10.1002/1873-3468.13763

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 a1- and b-adrenoceptors (ARs) in hepatocytes. In isolated rat hepatocytes, stimulation of a1-AR increases H2O2 production via NADPH oxidase 2 (NOX2) activation. We find that the H2O2 thus produced is essential for a1-AR-mediated activation of the classical hepatic glycogenolytic, gluconeogenic, and ureagenic responses. However, H2O2 inhibits b-AR-mediated activation of these metabolic responses. We show that H2O2 mediates its effects on a1-AR and b-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 a1-AR in hepatocytes, which, by negatively regulating b-AR signaling, establishes negative crosstalk between the two pathways.

【 授权许可】

Unknown