TY  - JOUR
A1  - Meurer, Sabine
A1  - Pioch, Sylke
A1  - Pabst, Tatjana
A1  - Opitz, Nils
A1  - Schmidt, Peter M.
A1  - Beckhaus, Tobias
A1  - Wagner, Kristina
A1  - Matt, Simone
A1  - Gegenbauer, Kristina
A1  - Geschka, Sandra
A1  - Karas, Michael
A1  - Stasch, Johannes-Peter
A1  - Schmidt, Harald H. H. W.
A1  - Müller-Esterl, Werner
T1  - Nitric oxide-independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteosomal degradation
T2  - BMC pharmacology
N2  - Background: Nitric oxide (NO) is an essential vasodilator. In vascular diseases, oxidative stress attenuates NO signaling by both chemical scavenging of free NO and oxidation and down-regulation of its major intracellular receptor, the alpha/beta heterodimeric heme-containing soluble guanylate cyclase (sGC). Oxidation can also induce loss of sGC's heme and responsiveness to NO.
Results: sGC activators such as BAY 58-2667 bind to oxidized/heme-free sGC and reactivate the enzyme to exert disease-specific vasodilation. Here we show that oxidation-induced down-regulation of sGC protein extends to isolated blood vessels. Mechanistically, degradation was triggered through sGC ubiquitination and proteasomal degradation. The heme-binding site ligand, BAY 58-2667, prevented sGC ubiquitination and stabilized both alpha and beta subunits.
Conclusion: Collectively, our data establish oxidation-ubiquitination of sGC as a modulator of NO/cGMP signaling and point to a new mechanism of action for sGC activating vasodilators by stabilizing their receptor, oxidized/heme-free sGC.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7087
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-70854
SN  - 1471-2210
N1  - © 2009 Meurer et al; licensee BioMed Central Ltd.
VL  - 9
IS  - (Suppl 1):P49
SP  - 1
EP  - 1
PB  - BioMed Central
CY  - London
ER  -