C-type natriuretic peptide decreases soluble guanylate cyclase levels by activating the proteasome pathway
Authors
Frutos García, Sergio de; Rodríguez Puyol, Diego María; Rodríguez Puyol, Manuel Antonio; Saura Redondo, Marta; Rivero Vilches, Francisco JavierIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/60941DOI: 10.1016/j.bbamcr.2003.10.003
ISSN: 0167-4889
Date
2003-12-01Affiliation
Universidad de Alcalá. Departamento de Biología de Sistemas; Universidad de Alcalá. Departamento de Medicina y Especialidades MédicasBibliographic citation
Biochimica et Biophysica Acta - Molecular Cell Research, 2003, v. 1643, n. 1-3, p. 105-112
Keywords
Soluble guanylate cyclase
Particulate guanylate cyclase
Cross-regulation
Protein degradation
Proteasome
cGMP
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/aceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
© Elsevier
Access rights
info:eu-repo/semantics/openAccess
Abstract
Natriuretic peptides (NP) activate particulate guanylate cyclase (pGC) and nitric oxide (NO) activates soluble guanylate cyclase (sGC). Both guanylate cyclases catalyse the formation of the same second messenger, cyclic guanosine 3′,5′-monophosphate (cGMP), which activates the cGMP-dependent protein kinases (PKG). PKG then starts a signalling cascade that mediates many cardiovascular and renal effects, such as smooth muscle relaxation and diuresis. Many cell types possess both sGC and pGC. Because both GC-cGMP systems play complementary roles, an interaction between the two pathways might represent an important physiological control mechanism. In this report we demonstrate an interaction between the two pathways. C-type natriuretic peptide (CNP) decreased the beta-subunit of sGC (sGC-beta) steady-state protein levels and enzymatic activity in cultured human mesangial cells (HMC) in a time- and dose-dependent manner. This down-regulation was not dependent on changes in sGC-beta mRNA levels. Treatment of the cells with the stable cGMP analogue 8-Br-cGMP or the phosphodiesterase type-5 inhibitor Zaprinast produced the same down-regulatory effect. Inhibition of PKG or proteasome activity prevented the CNP-induced reduction of sGC-beta protein levels and activity. Taken together, these results demonstrate that pGC activation induces a post-transductional down-regulation of sGC by a mechanism involving PKG and the proteasome pathway.
Files in this item
Files | Size | Format |
|
---|---|---|---|
Frutos_CType_BioBioActa_2003.pdf | 641.4Kb |
|
Files | Size | Format |
|
---|---|---|---|
Frutos_CType_BioBioActa_2003.pdf | 641.4Kb |
|
Collections
- FISIOLOG - Artículos [87]