AUTHOR=Steinberg Susan F. 

TITLE=Redox and proteolytic regulation of cardiomyocyte β1-adrenergic receptors – a novel paradigm for the regulation of catecholamine responsiveness in the heart

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1306467

DOI=10.3389/fimmu.2023.1306467

ISSN=1664-3224

ABSTRACT=<p>Conventional models view β<sub>1</sub>-adrenergic receptors (β<sub>1</sub>ARs) as full-length proteins that activate signaling pathways that influence contractile function and ventricular remodeling - and are susceptible to agonist-dependent desensitization. This perspective summarizes recent studies from my laboratory showing that post-translational processing of the β<sub>1</sub>-adrenergic receptor N-terminus results in the accumulation of both full-length and N-terminally truncated forms of the β<sub>1</sub>AR that differ in their signaling properties. We also implicate oxidative stress and β<sub>1</sub>AR cleavage by elastase as two novel mechanisms that would (in the setting of cardiac injury or inflammation) lead to altered or decreased β<sub>1</sub>AR responsiveness.</p>