Dietary Interaction of High Fat and Marginal Copper Deficiency on Cardiac Contractile Function*

Obesity ◽  
2007 ◽  
Vol 15 (5) ◽  
pp. 1242-1257 ◽  
Author(s):  
David P. Relling ◽  
Lucy B. Esberg ◽  
W. Thomas Johnson ◽  
Eric J. Murphy ◽  
Edward C. Carlson ◽  
...  
Keyword(s):  
Copper Deficiency ◽  
Contractile Function ◽  
High Fat ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Dietary Interaction

Isolated ventricular myocytes from copper-deficient rat hearts exhibit enhanced contractile function

2001 ◽  
Vol 281 (2) ◽  
pp. H476-H481 ◽  
Author(s):  
Loren E. Wold ◽  
Jack T. Saari ◽  
Jun Ren
Keyword(s):  
Cardiac Fibrosis ◽  
Copper Deficiency ◽  
Ventricular Myocytes ◽  
Contractile Function ◽  
Detection System ◽  
Cardiac Contractile Function ◽  
Acetoxymethyl Ester ◽  
Cardiac Contractile ◽  
Rat Hearts ◽  
Intracellular Ca

Dietary copper deficiency leads to cardiac hypertrophy, cardiac fibrosis, derangement of myofibrils, and impaired cardiac contractile and electrophysiological function. The purpose of this study was to determine whether impaired cardiac function from copper deficiency is due to depressed contractile function at the single myocyte level. Male Sprague-Dawley rats were fed diets that were either copper adequate (5.59–6.05 μg copper/g body wt; n = 11) or copper deficient (0.29–0.34 μg copper/g body wt; n = 11) for 5 wk. Ventricular myocytes were dispersed and mechanical properties were evaluated using the SoftEdge video-based edge-detection system. Intracellular Ca2+ transients were examined using fura 2-acetoxymethyl ester. Myocytes were electrically stimulated to contract at 0.5 Hz. Properties evaluated included peak shortening (PS), time to peak shortening (TPS), time to 90% relengthening (TR90), and maximal velocities of shortening and relengthening (±d L/d t). Myocytes from the copper-deficient rat hearts exhibited significantly enhanced PS values associated with shortened TR90 measurements compared with those from copper-adequate rat hearts. The ±d L/d t values were enhanced and the intracellular Ca2+ transient decay rate was depressed in myocytes from copper-deficient rats. These data indicate that impaired cardiac contractile function that is seen in copper-deficient whole hearts might not be due to depressed cardiac contractile function at the single cell level but rather to other mechanisms such as cardiac fibrosis.

Cytokines and Cardiac Contractile Function

Circulation ◽  
1997 ◽  
Vol 95 (4) ◽  
pp. 778-781 ◽  
Author(s):  
Ralph A. Kelly ◽  
Thomas W. Smith
Keyword(s):  
Contractile Function ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile

scholarly journals Regulation of Cardiac PKA Signaling by cAMP and Oxidants

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 663
Author(s):  
Friederike Cuello ◽  
Friedrich W. Herberg ◽  
Konstantina Stathopoulou ◽  
Philipp Henning ◽  
Simon Diering
Keyword(s):  
Contractile Function ◽  
Cardiac Contractility ◽  
Cellular Protein ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Main Driver ◽  
Dependent Protein ◽  
Relevant Regulation ◽  
Protein Dysfunction ◽  
Substrate Proteins

Pathologies, such as cancer, inflammatory and cardiac diseases are commonly associated with long-term increased production and release of reactive oxygen species referred to as oxidative stress. Thereby, protein oxidation conveys protein dysfunction and contributes to disease progression. Importantly, trials to scavenge oxidants by systemic antioxidant therapy failed. This observation supports the notion that oxidants are indispensable physiological signaling molecules that induce oxidative post-translational modifications in target proteins. In cardiac myocytes, the main driver of cardiac contractility is the activation of the β-adrenoceptor-signaling cascade leading to increased cellular cAMP production and activation of its main effector, the cAMP-dependent protein kinase (PKA). PKA-mediated phosphorylation of substrate proteins that are involved in excitation-contraction coupling are responsible for the observed positive inotropic and lusitropic effects. PKA-actions are counteracted by cellular protein phosphatases (PP) that dephosphorylate substrate proteins and thus allow the termination of PKA-signaling. Both, kinase and phosphatase are redox-sensitive and susceptible to oxidation on critical cysteine residues. Thereby, oxidation of the regulatory PKA and PP subunits is considered to regulate subcellular kinase and phosphatase localization, while intradisulfide formation of the catalytic subunits negatively impacts on catalytic activity with direct consequences on substrate (de)phosphorylation and cardiac contractile function. This review article attempts to incorporate the current perception of the functionally relevant regulation of cardiac contractility by classical cAMP-dependent signaling with the contribution of oxidant modification.

scholarly journals Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

2009 ◽  
Vol 297 (3) ◽  
pp. R682-R689 ◽  
Author(s):  
Yinan Hua ◽  
Heng Ma ◽  
Willis K. Samson ◽  
Jun Ren
Keyword(s):  
Contractile Function ◽  
Peptide Hormone ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Cardiac Contractile Function ◽  
Mechanical Responses ◽  
Cardiac Contractile ◽  
Short Term Exposure ◽  
The Impact ◽  
Dependent Mechanism

Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (±dP/d t), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/d t) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 μM) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM). The PKC inhibitor chelerythrine (1 μM) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA- and/or JNK-dependent mechanism.

Abstract 355: Exercise Prevents Doxorubicin-induced Cardiotoxicity via Targeting Microrna-669a-5p in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yihua Bei ◽  
Jiahong Xu ◽  
Tianzhao Xu ◽  
Ping Chen ◽  
Lin Che ◽  
...  
Keyword(s):  
Protective Effect ◽  
Target Gene ◽  
Contractile Function ◽  
Cardiac Contractile Function ◽  
Downstream Target ◽  
Cardiac Contractile ◽  
Downstream Target Gene ◽  
Cardiac Ejection Fraction ◽  
Response To Exercise ◽  
Fractional Shortening

Doxorubicin (Dox)-induced cardiotoxicity, usually associated with increased oxidative stress, myofibrillar deterioration, and impaired cardiac contractile function, is a serious complication of antitumor therapy which may not be detected for many years. Growing evidence indicates that the regulation of cardiac microRNA (miRNA, miR) in response to exercise is essentially involved in the protective effect of exercise in the treatment of cardiovascular diseases. However, it is largely unknown whether and how exercise could prevent Dox-induced cardiotoxicity via regulating miRNA biology. In the current study, C57BL/6 mice were either subjected to a 3-week swimming program or remained sedentary. Mice were then treated with Dox (ip. 4 mg/kg/week for 4 weeks) to induce cardiotoxicity. Our data demonstrated that Dox resulted in marked reduction of cardiac ejection fraction (EF, %) and fractional shortening (FS, %) as measured by echocardiography. Interestingly, exercise significantly improved cardiac EF (%) and FS (%) in Dox-treated mice, indicating the protective effect of exercise in Dox-induced cardiotoxicity. Then, we performed microarray analysis (Affymetrix 3.0) showing that miR-27a-5p, miR-34b-3p, miR-185-3p, miR-203-3p, miR-669a-5p, miR-872-3p, and let-7i-3p were significantly reduced, while miR-2137 was increased in the hearts of exercised Dox-treated mice versus sedentary Dox-treated mice (FC(abs)>1.5, p<0.05). Using qRT-PCR, we further verified that miR-669a-5p was reduced by exercise training in Dox-treated mice. These data reveal that miR-669a-5p might be a potential miRNA mimicking the benefit of exercise in Dox-induced cardiotoxicity. Further study is needed to clarify the functional effect of miR-669a-5p and to identify its downstream target gene that contributes to the prevention and treatment of Dox-induced cardiotoxicity.

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