Prevention of PKG-1α Oxidation Suppresses Antihypertrophic/Antifibrotic Effects From PDE5 Inhibition but not sGC Stimulation.

ABSTRACT:

Background

Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation.

Methods and results

Knock-in mice expressing a redox-dead PKG1α (PKG1α^C42S) or littermate controls (PKG1α^WT) were subjected to transaortic constriction to induce pressure overload and treated with a PDE5 i

SUBMITTER: Nakamura T 

PROVIDER: S-EPMC5858464 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature