Cyclic GMP-Induced Reduction in Cardiac Myocyte Function Is Partially Mediated by Activation of the Sarcoplasmic Reticulum Ca&lt;sup&gt;2+&lt;/sup&gt;-ATPase

Zhang, Qihang; Yan, Lin; Weiss, Harvey R.; Scholz, Peter

doi:10.1159/000056158

Cited by 21 publications

(20 citation statements)

References 36 publications

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“…The integrated reduction in myofibril contractility, induced by cGMP in response to metabolic stress, decreases tissue indices of energy demand, including force of contraction (31), tension (32), fractional shortening (33), and maximum rate of shortening (34).…”

Section: Resultsmentioning

confidence: 99%

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism

Ruiz-Stewart

Tiyyagura

Lin

et al. 2003

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

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Defending cellular integrity against disturbances in intracellular concentrations of ATP ([ATP]M etabolically active cells with high-energy requirements are particularly susceptible to structural and functional impairment when deprived of oxygen and substrates obligatory for generating ATP (1, 2). Maintenance of homeostasis requires these cells to respond to rapidly fluctuating energy demands in the context of varying supplies of metabolic substrates. Tight coordination between energy supply and demand is predicated on efficient communication and integration between metabolism, the steady-state and local availability of high-energy phosphates, and signaling mechanisms regulating cell functions. Although specific components and their interactions that transduce metabolic and energetic signaling have been described (1), molecular mechanisms mediating their coordination with cellular signaling remain incompletely understood.Production and release of NO represents one paracrine͞ autocrine mechanism coordinating energy supply and demand in tissues. Metabolic stress, such as ischemia, stimulates NO synthases to produce NO from arginine (3). In turn, NO regulates the supply of energy by improving the delivery of substrates and oxygen to deprived tissues (4-6), regulating the intracellular delivery of metabolic substrates (7-10), selection of substrates that support metabolism (6, 10-14), oxidation of metabolic substrates (15), generation of ATP by improving metabolic efficiency (16), and biogenesis of mitochondria (17). Conversely, NO reduces the demand for ATP by decreasing energyconsuming cell functions, for example, by reducing the activity of the contractile apparatus in muscle cells (ref. 18 and references therein). Moreover, in some models of severe hypoxic stress, NO induces complete and reversible metabolic stasis required to survive the insult (19). The importance of NO in defending against ischemia is underscored by its regulation of the transcription factor hypoxia inducible factor 1, a master regulator of cellular homeostasis in the context of oxygen insufficiency (20).Coordination of energy supply and demand is mediated, in part, by NO activation of soluble guanylyl cyclase (sGC) and the associated accumulation of intracellular cGMP concentration ([cGMP] i ) (9,10,12,15,16,18), yet the mechanisms coordinating cGMP-dependent and metabolic signaling, beyond the production of NO, remain undefined. Recently, a novel mechanism was identified by which adenine nucleotides inhibit GCs (21,22) that is analogous to P site inhibition of adenylyl cyclases (23). Indeed, the two-substituted adenine nucleotides 2-methylthio-ATP and 2-chloro-ATP inhibit NO-dependent cGMP production by directly binding to sGC (22). Synthetic two-substituted adenine nucleotides presumably exploit allosteric mechanisms regulated by endogenous cell products. The present study revealed that ATP is the native ligand mediating adenine nucleotide-dependent inhibition of sGC by binding directly to an allosteric purinergic site on the enzyme. More...

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Section: Resultsmentioning

confidence: 99%

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism

Ruiz-Stewart

Tiyyagura

Lin

et al. 2003

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

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“…This is coincided with the notion that sustained cellular cGMP induces apoptosis, delays cell cycle progression and usually produces negative functional and metabolic effects on cardiomyocytes. 22) Perturbations in mitochondrial physiology appear to play an important role in apoptosis. 23) Commonly, Dy m dissipation is triggered by permeability transition pore (PT pore) opening and then cells lose the ability to synthesis of mitochondrial ATP.…”

Section: Discussionmentioning

confidence: 99%

B-Type Natriuretic Peptide Enhances Mild Hypoxia-Induced Apoptotic Cell Death in Cardiomyocytes

Wang

et al. 2007

Biological & Pharmaceutical Bulletin

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The natriuretic peptides are a family of small peptides that activates specific NP-bound guanylyl cyclase (GC) receptors and stimulates cGMP synthesis. Three main natriuretic peptides have been identified so far: atrial (ANP), B-type (BNP) and C-type natriuretic peptides (CNP). Among them, BNP having a common core structure of natriuretic peptides, which consists a 17-member disulfide ring with a highly conserved internal sequence of -FGXXXDRIGXXSGL-, plays an essential role in the maintenance of homeostasis such as natriuresis, diuresis, vasorelaxant effect and inhibits the activation of renin-angiotensin-aldosterone system under pathological conditions. 1) Expression of the three natriuretic peptide receptors (NPR-A, NPR-B, NPR-C) has been confirmed in human and rat cardiac tissue.2) Commonly, BNP exhibits its effects by preferentially binding to the NPR-A (also known as GC-A) which is coupled to cytoplasmic C-terminal GC catalytic domain and signals via formation of cGMP. 3,4) Although some studies have shown a compensatory role for BNP in heart disease, the precise contribution of BNP to the pathophysiology of heart is poorly understood.Ischemia is one of the most common pathological conditions in many cardiovascular diseases. Apoptotic cell death has been shown to be one of the major pathological events in a variety of cardiovascular ischemic conditions such as myocardial infarction.5) As the stimuli of cardiomyocyte apoptosis, a range of stress including mild hypoxic, 6) ischemic and neurohumoral stimulation 7) has been illustrated in vitro. Particularly in several studies, hypoxia is the direct trigger and well-known stimulus of apoptosis independent of the neuronhumoral factors in various physiologic and pathologic conditions.8) Some studies have indicated that ANP and CNP inhibit vascular smooth muscle growth [9][10][11] and ANP induces apoptosis in cultured vascular smooth muscle cells, 12) which infer the negative effect of natriuretic peptides on the cardiovascular system. In this regard, the role of BNP in mild hypoxia-induced cardiomyocytes apoptosis and the possible mechanism are of great interest to explore. The present study was therefore designed to examine whether BNP influenced apoptotic cardiomyocyte death under mild hypoxia which has been proved to trigger the intrinsic mitochondrial death signaling pathway, and whether cGMP was involved in the process. MATERIALS AND METHODSPrimary Culture of Cardiomyocytes Primary culture of neonatal rat cardiomyocytes were prepared as described before.13) In brief, the ventricles of 3-d-old Sprague-Dawley rats were digested with 0.08% trypsin and 0.06% collagenase II (Sigma Chemical Co., U.S.A.). The cells in suspension were collected, washed and seeded in 24 well plates at a density of 2ϫ10 5 cells. All cells were cultured in a medium containing 85% DMEM (Invitrogen, CA, U.S.A.) and 15% fetal bovine serum. The proportion of cardiomyocytes was enriched by the preplating method. BrdU (0.1 mM, Sigma, U.S.A.) was added within the first 48 h to inhibit fibrob...

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“…Previous studies in our laboratory suggested that cyclic GMP signaling affects myocyte function, in part, through phosphorylation of phospholamban, which regulates SERCA activity [2,5]. In the current study, we used a genetic approach using phospholamban knockout (PLB-KO) mouse myocytes to test the hypothesis that the negative functional effects of cyclic GMP on cardiac myocytes were mediated through cyclic GMP-dependent regulation of phospholamban (PLB) and subsequent changes in intracellular calcium transients.…”

Section: Introductionmentioning

confidence: 99%

“…Elevation in the level of cyclic GMP decreases myocyte oxygen consumption and myocyte contraction in rabbit, mouse and canine hearts and cardiac ventricular myocytes [2,3]. The negative effects of cyclic GMP are mainly mediated through the cyclic GMP-dependent protein kinase and this could reduce intracellular Ca 2+ by activation of the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA) [4,5]. Cyclic GMP mediated signaling may also involve phosphorylation of ryanodine receptors (RyRs) by cyclic GMP-dependent protein kinase and/or indirectly regulate RyRs by changing the cytosolic levels of RyRs through cADP-ribose [6].…”

Section: Introductionmentioning

confidence: 99%

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Role of Phospholamban in Cyclic GMP Mediated Signaling in Cardiac Myocytes

Zhang¹,

Scholz

Pilzak

et al. 2007

Cell Physiol Biochem

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We tested the hypothesis that the negative functional effects of cyclic GMP on cardiac myocytes were mediated through phospholamban (PLB) and activation of sarcoplasmic reticulum Ca²⁺-ATPase. Using ventricular myocytes from wild type (WT, n=10) and PLB knockout (PLB-KO, n=10) mouse hearts, functional changes were measured using a video edge detector at baseline and after 10^-6, 10^-5M 8-bromo-cyclic GMP (cGMP), 10^-8, 10^-7M C-type natriuretic peptide (CNP), or 10^-6, 10^-5M S-nitroso-N-acetyl-penicillamine (SNAP, nitric oxide donor). Changes in cytosolic Ca²⁺ concentration were assessed in fura 2-loaded WT and PLB-KO myocytes. Cyclic GMP dependent phosphorylation analysis was also performed in WT and PLB-KO myocytes. 8-bromo-cGMP 10^-5M caused a significant decrease in %shortening (3.6±0.2% to 2.3±0.1%) in WT, but little change in PLB-KO myocytes (3.4±0.1% to 3.2±0.2%). Similarly, CNP and SNAP reduced %shortening of WT, but not PLB-KO myocyte. Changes in other contractile parameters such as maximum rate of shortening and relaxation were consistent with the changes in % shortening. Intracellular Ca²⁺ transients changed similarly to cell contractility in WT and PLB-KO myocytes treated with cGMP and CNP; i.e. Ca²⁺ transients decreased with cGMP or CNP in WT myocytes, but were unchanged in PLB-KO myocytes. cGMP dependent phosphorylation analysis showed that some proteins were phosphorylated by cGMP to a lesser extent in PLB-KO compared with WT myocytes, suggesting impaired cGMP-kinase function in PLB-KO cardiac myocytes. These results indicated that cGMP-induced reductions in cardiac myocyte function were at least partially mediated through the action of phospholamban.

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Cyclic GMP-Induced Reduction in Cardiac Myocyte Function Is Partially Mediated by Activation of the Sarcoplasmic Reticulum Ca<sup>2+</sup>-ATPase

Cited by 21 publications

References 36 publications

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism

Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism

B-Type Natriuretic Peptide Enhances Mild Hypoxia-Induced Apoptotic Cell Death in Cardiomyocytes

Role of Phospholamban in Cyclic GMP Mediated Signaling in Cardiac Myocytes

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