Phospholamban S-nitrosylation modulates Starling response in fish heart

ISO-and endothelin-1-induced positive inotropism and coronary constriction . Thus, besides its antihypertensive properties, CST is now emerging as a novel cardiac modulator, which would protect the heart against excessive systemic and/or intra-cardiac excitatory stimuli (e.g. catecholamines and endothelin-1). Accepted 4 August 2010 SUMMARY Catestatin (CST), the 21-amino acid, cationic and hydrophobic peptide proteolytically derived from the ubiquitous chromogranin A (CgA), is an endogenous inhibitor of catecholamine release, a potent vasodilator in vivo and an anti-hypertensive agent in mammals, including humans. Recently, we discovered that CST also functions as an important negative modulator of heart performance in frog and rat. To gain an evolutionary perspective on CST cardiotropism in fish, we analysed the influence of bovine CST (CgA 344-364 ) on the eel heart, as well as the eventual species-specific mechanisms of its myocardial action. Experiments were carried out on fresh-water eels (Anguilla anguilla L.) using an electrically paced isolated working heart preparation.

Section: Frank-starling Responsesupporting

confidence: 81%

Section: Frank-starling Response and Cst Signal Transductionmentioning

confidence: 99%

Section: Frank-starling Responsementioning

confidence: 99%

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The catecholamine release-inhibitory peptide catestatin (chromogranin A344-364) modulates myocardial function in fish

Imbrogno

Garofalo

Cerra

et al. 2010

“…In goldfish, the expression of Mb in the heart does not change with hypoxia (Roesner et al, 2008) and the Mb O 2 affinity may be so high that Mb does not deoxygenate sufficiently at the prevailing tissue P O2 to generate enough NO (and N 2 O 3 ) to maintain S-nitrosylation of proteins. This may be of significance, because S-nitrosylation of proteins has been reported to modulate the inotropic response of fish hearts (Garofalo et al, 2009). …”

Section: Influence Of Hypoxia On No Metabolitesmentioning

confidence: 99%

Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

Hansen

Frank

2010

SUMMARYNitric oxide (NO), produced by nitric oxide synthases (NOS enzymes), regulates multiple physiological functions in animals. NO exerts its effects by binding to iron (Fe) of heme groups (exemplified by the activation of soluble guanylyl cyclase) and by Snitrosylation of proteins -and it is metabolized to nitrite and nitrate. Nitrite is used as a marker for NOS activity but it is also a NO donor that can be activated by various cellular proteins under hypoxic conditions. Here, we report the first systematic study of NO metabolites (nitrite, nitrate, S-nitroso, N-nitroso and Fe-nitrosyl compounds) in multiple tissues of a non-mammalian vertebrate (goldfish) under normoxic and hypoxic conditions. NO metabolites were measured in blood (plasma and red cells) and heart, brain, gill, liver, kidney and skeletal muscle, using highly sensitive reductive chemiluminescence. The severity of the chosen hypoxia levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at P O2 (partial pressure of O 2 ) values close to and below the critical P O2 ] for two days caused large decreases in plasma nitrite and nitrate, which suggests reduced NOS activity and increased nitrite/nitrate utilization or loss. Tissue NO metabolites were largely maintained at their tissue-specific values under hypoxia, pointing at nitrite transfer from extracellular to intracellular compartments and cellular NO generation from nitrite. The data highlights the preference of goldfish to defend intracellular NO homeostasis during hypoxia.

“…This involves a protein kinase B (Akt)-mediated activation of 'eNOS-like'-dependent NO production, which, acting through a non-classical cGMPindependent pathway, induces a phospholamban (PLN)-Snitrosylation-dependent increase of sarcoplasmic reticulum (SR)-Ca 2+ reuptake ( Fig.2) (Garofalo et al, 2009; Cerra and Imbrogno, 2012).…”

Section: Intrinsic Regulation: the Frank-starling Responsementioning

confidence: 99%

The eel heart: multilevel insights into functional organ plasticity

Imbrogno

2013

SummaryThe remarkable functional homogeneity of the heart as an organ requires a well-coordinated myocardial heterogeneity. An example is represented by the selective sensitivity of the different cardiac cells to physical (i.e. shear stress and/or stretch) or chemical stimuli (e.g. catecholamines, angiotensin II, natriuretic peptides, etc.), and the cell-specific synthesis and release of these substances. The biological significance of the cardiac heterogeneity has recently received great attention in attempts to dissect the complexity of the mechanisms that control the cardiac form and function. A useful approach in this regard is to identify natural models of cardiac plasticity. Among fishes, eels (genus Anguilla), for their adaptive and acclimatory abilities, represent a group of animals so far largely used to explore the structural and ultrastructural myoarchitecture organization, as well as the complex molecular networks involved in the modulation of the heart function, such as those converting environmental signals into physiological responses. However, an overview on the existing current knowledge of eel cardiac form and function is not yet available. In this context, this review will illustrate major features of eel cardiac organization and pumping performance. Aspects of autocrine-paracrine modulation and the influence of factors such as body growth, exercise, hypoxia and temperature will highlight the power of the eel heart as an experimental model useful to decipher how the cardiac morpho-functional heterogeneities may support the uniformity of the whole-organ mechanics.Key words: autocrine/paracrine regulation, contractility and relaxation, Frank-Starling response, neuro-humoral modulation, sarcoplasmic reticulum, transduction cascades. all levels of cardiac organization from gross morphology to molecular biology (Katz and Katz, 1989). As illustrated by Olson (Olson, 2006), this results from the modular morphogenesis of the heart driven by distinct transcriptional regulatory programs. Hopefully, this review may also help to illustrate how the fish heart, like all vertebrate hearts, accomplishes a multilevel physiological integration, i.e. homogeneity of function, compensating for its morpho-functional heterogeneity.I also wish to emphasize that, due to their commercial value and laboratory amenability, many eel species are now considered critically endangered, thereby calling for ethical considerations. This would imply a critical decision when choosing this animal as an experimental model for biomedical research. Cardiac morphological designThe eel heart consists of four chambers placed in series: a sinus venosus, a thin-walled atrium, a more muscular ventricle and an outflow tract (bulbus arteriosus) (Fig.1). The peripheral venous blood flows in sequence from the sinus venosus to the atrium, to the ventricle and to the bulbus arteriosus, from where it is pumped to the gills to be oxygenated and then distributed to the body, reflowing to the heart. The sinus venosus is a large chamber separated fr...