TY  - JOUR
A1  - Meurer, Sabine
A1  - Pabst, Tatjana
A1  - Pioch, Sylke
A1  - Opitz, Nils
A1  - Schmidt, Peter M.
A1  - Wagner, Kristina
A1  - Matt, Simone
A1  - Schmidt, Harald H. H. W.
A1  - Müller-Esterl, Werner
T1  - Oxidative stress induces CHIP-mediated ubiquitination and roteasomal degradation of soluble guanylyl cyclase : oral presentation
T2  - BMC pharmacology
N2  - Oxidative stress attenuates the NO-cGMP pathway, e.g. in the vascular system, through scavenging of free NO radicals by superoxide O2•-, by inactivation of soluble guanylyl cyclase (sGC) via oxidation of its central Fe2+ ion, and by down-regulation of sGC protein levels. While the former pathways are well established, the molecular mechanisms underlying the latter are still obscure. Using oxidative sGC inhibitor ODQ we demonstrate rapid down-regulation of sGC protein in mammalian cells. Co-incubation with proteasomal inhibitor MG132 results in accumulation of ubiquitinated sGC whereas sGC activator BAY 58–2667 prevents ubiquitination. ODQ-induced down-regulation of sGC is mediated through selective ubiquitination of its b subunit, and BAY 58–2667 abrogates this effect. Ubiquitination of sGC-b is dramatically enhanced by E3 ligase CHIP. Our data indicate that oxidative stress promotes ubiquitination of sGC b subunit through E3 ligase CHIP, and that sGC activator 58–2667 reverts this effect, most likely through stabilization of the heme-free b subunit. Thus the deleterious effects of oxidative stress can be counter-balanced by an activator of a key enzyme of vascular homeostasis.
Y1  - 2007
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/727
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-47192
N1  - © 2007 Meurer et al; licensee BioMed Central Ltd.
VL  - 7(Suppl 1)
IS  - S34
SP  - 1
EP  - 1
ER  -