Cyclic Nucleotide Phosphodiesterase PDE1C1 in Human Cardiac Myocytes

Vandeput, Fabrice; Wolda, Sharon L.; Krall, John M.; Hambleton, Ryan; Uher, L.; McCaw, Kim N.; Radwański, Przemysław; Florio, Vincent A.; Movsesian, Matthew A.

doi:10.1074/jbc.m703173200

Cited by 99 publications

(109 citation statements)

References 52 publications

(27 reference statements)

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…This is presumed to be attributable to increased cGMP in one or more compartments in the heart. It has been shown that these same concentrations of SIL also inhibit PDE-1C activity by ∼20% in heart extracts (58). It is also reported that SIL treatment increases cardiac cGKI activity efficiently, although it is not clear that this occurs in the CM (34).…”

Section: Discussionmentioning

confidence: 97%

Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes

Łukowski

Rybalkin

Loga

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

View full text Add to dashboard Cite

It has been suggested that cGMP kinase I (cGKI) dampens cardiac hypertrophy. We have compared the effect of isoproterenol (ISO) and transverse aortic constriction (TAC) on hypertrophy in WT [control (CTR)] mice, total cGKI-KO mice, and cGKIβ rescue mice (βRM) lacking cGKI specifically in cardiomyocytes (CMs). Infusion of ISO did not change the expression of cGKI in the hearts of CTR mice or βRM but raised the heart weight by ∼20% in both. An identical hypertrophic growth response was measured in CMs from CTR mice and βRM and in isolated adult CMs cultured with or without 1 μM ISO. In both genotypes, ISO infusion induced similar changes in the expression of hypertrophy-associated cardiac genes and significant elevation of serum atrial natriuretic peptide and total cardiac cGMP. No differences in cardiac hypertrophy were obtained by 7-day ISO infusion in 4-to 6-week-old conventional cGKI-KO and CTR mice. Furthermore, TAC-induced hypertrophy of CTR mice and βRM was not different and did not result in changes of the cGMP-hydrolyzing phosphodiesterase activities in hypertropic hearts or CMs. These results strongly suggest that cardiac myocyte cGKI does not affect the development of heart hypertrophy induced by pressure overload or chronic ISO infusion.cyclic nucleotides | phosphodiesterase | phosphorylation | transverse aortic constriction | sildenafil C linical studies and genetically modified mice have supported the notion that natriuretic peptides (NPs), the particulate guanylyl cyclase (GC)-A, and the second messenger cGMP can attenuate the development of pressure-or volume-induced cardiac hypertrophy and fibrosis (1). Disruption of the murine GC-A gene, the receptor for the cardiac "hormones" atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), results in salt-resistant elevation of blood pressure, cardiac fibrosis, and hypertrophy (2, 3). To a great extent, hypertrophy is independent of blood pressure elevation (4, 5) but is enhanced transverse aortic constriction (TAC) in the absence of GC-A (4). Further studies using cardiac muscle-specific deletion of GC-A confirmed that cardiac muscle hypertrophy is independent of changes in blood pressure (6). ANP, nitric oxide (NO) donors, and 8-Br-cGMP inhibited norepinephrine-induced hypertrophy of cardiac cells and fibroblasts (7,8).Although it is recognized that GC-A-deficient hearts exhibit marked hypertrophy with interstitial fibrosis (2, 9), deletion of ANP did not result in obvious hypertrophy and fibrosis (10). Other reports have indicated that ANP ablation in mice causes an accelerated susceptibility to hypertrophy induced by different stress stimuli (11,12). Obviously, ANP and BNP secreted by the cardiomyocytes (CMs) act as paracrine factors that exert antifibrotic effects in vivo and play a role as local regulators of ventricular remodeling. Furthermore, it has been shown that rats expressing a dominant-negative mutant of GC-B and having an attenuated cGMP response to C-natriuretic peptide and a normal response to ANP showed marked cardiac hyp...

show abstract

Section: Discussionmentioning

confidence: 97%

Cardiac hypertrophy is not amplified by deletion of cGMP-dependent protein kinase I in cardiomyocytes

Łukowski

Rybalkin

Loga

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

137

View full text Add to dashboard Cite

show abstract

“…A PDE1-selective inhibitor (IC86340) blunts the hypertrophic response. These results are highly relevant since PDE1 provides the majority of cGMP-hydrolyzing activity in the heart (259,388,389,395) and acts to counter the cytoprotective effects of cGMP signaling through cGMP-dependent protein kinase (PKG).…”

Section: Calmodulin-binding Phosphodiesterases (Pde1)mentioning

confidence: 99%

“…Vinpocetine, the best known PDE1 inhibitor, has been used clinically in some places but has poor cell penetration properties and a significant toxicity profile. Most PDE5-selective inhibitors also inhibit PDE1, which becomes problematic when high extracellular concentrations are used (388,389). ICOS Corporation (now a part of Eli Lilly Corporation) has produced two selective and potent PDE1 inhibitors (IC229 and IC224 with IC 50 values of 560 and 800 nM, respectively) (249, 388, 389).…”

Section: Pde1 Inhibitorsmentioning

confidence: 99%

Mammalian Cyclic Nucleotide Phosphodiesterases: Molecular Mechanisms and Physiological Functions

Francis

Blount

Corbin

2011

Physiological Reviews

560

546

View full text Add to dashboard Cite

The superfamily of cyclic nucleotide (cN) phosphodiesterases (PDEs) is comprised of 11 families of enzymes. PDEs break down cAMP and/or cGMP and are major determinants of cellular cN levels and, consequently, the actions of cN-signaling pathways. PDEs exhibit a range of catalytic efficiencies for breakdown of cAMP and/or cGMP and are regulated by myriad processes including phosphorylation, cN binding to allosteric GAF domains, changes in expression levels, interaction with regulatory or anchoring proteins, and reversible translocation among subcellular compartments. Selective PDE inhibitors are currently in clinical use for treatment of erectile dysfunction, pulmonary hypertension, intermittent claudication, and chronic pulmonary obstructive disease; many new inhibitors are being developed for treatment of these and other maladies. Recently reported x-ray crystallographic structures have defined features that provide for specificity for cAMP or cGMP in PDE catalytic sites or their GAF domains, as well as mechanisms involved in catalysis, oligomerization, autoinhibition, and interactions with inhibitors. In addition, major advances have been made in understanding the physiological impact and the biochemical basis for selective localization and/or recruitment of specific PDE isoenzymes to particular subcellular compartments. The many recent advances in understanding PDE structures, functions, and physiological actions are discussed in this review.

show abstract

“…15 There are 3 isoforms (PDE1A, PDE1B and PDE1C), all expressed in cardiac myocytes. 16,17 PDE1A and PDE1B hydrolyze cGMP with higher affinity than cAMP, whereas PDE1C, the dominant isoform in human cardiac myocytes, hydrolyzes both with similar affinity. 17 Although PDE1 is a major esterase for both cAMP and cGMP in the myocardium or cardiac myocytes in humans, 16,18 its physiological effect, particularly in vivo, has not been fully clarified.…”

Section: Degradation By Pdesmentioning

confidence: 99%