Dataset Information

Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase 2A signaling in cardiac myocytes by nitroxyl

ABSTRACT: Sympathetic activation is the main driver of cardiac inotropy and lusitropy. Stimulation of the -adrenoceptor (AR) signaling cascade leads to activation of cAMP-dependent protein kinase (PKA) and subsequent cardiac protein phosphorylation, which is counteracted by the corresponding protein phosphatases 2A (PP2A). Both, kinase and phosphatase are sensitive to oxidation. For PKA, the oxidant-mediated mode of regulation has been described to occur by interdisulfide formation between type I regulatory subunits (PKA-RI). Furthermore, oxidant-mediated intradisulfide formation in the catalytic subunit of PKA and PP2A was shown to inhibit kinase or phosphatase activity, respectively. Nitroxyl donors exert positive inotropic and lusitropic effects in cardiac myocytes.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Regular Ventricular Cardiac Myocyte

SUBMITTER: Christoph Krisp