Internalized β2-Adrenergic Receptors Inhibit Subcellular Phospholipase C-Dependent Cardiac Hypertrophic Signaling.

ABSTRACT: Chronically elevated neurohumoral drive, and particularly elevated adrenergic tone leading to β-adrenergic receptor (β-AR) overstimulation in cardiac myocytes, is a key mechanism involved in the progression of heart failure. β1-AR and β2-ARs are the two major subtypes of β-ARs present in the human heart, however, they elicit different or even opposite effects on cardiac function and hypertrophy. For example, chronic activation of β1ARs drives detrimental cardiac remodeling while β2AR signaling is protective. The underlying molecular mechanisms for cardiac protection through β2ARs remain unclear. Here we show that β2-AR protects against hypertrophy through inhibition of PLCε signaling at the Golgi apparatus. The mechanism for β2AR-mediated PLC inhibition requires internalization of β2AR, ac

SUBMITTER: Wei W 

PROVIDER: S-EPMC10274790 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature