Functional significance of alterations in cardiac contractile protein isoforms

Kitsis, Richard N.; Scheuer, James

doi:10.1002/clc.4960190105

Cited by 12 publications

(5 citation statements)

References 112 publications

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“…Comprehensive studies of the role of gene expression in the development of cardiac hypertrophy and HF led to a conclusion that expression of latent genes encoding all three cardiomyocyte systems responsible for the contraction-relaxation cycle is a physiological adaptive phenomenon, rather than the cause of HF development [93,106,128].…”

Section: Causes Of Changes In Submolecular Actomyosin Structure In Hfmentioning

confidence: 99%

Energy, structure, conformation, and heart failure

Карсанов¹

1999

Bull Exp Biol Med

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The problem of heart failure is analyzed from the point of view of conformation changes in submolecular cardiomyocyte structures. The development of heart failure as a consequence of abnormal function of contractile myocardial proteins is discussed. The properties of actin and the role of structural changes in actin molecules in the impairment of ATP energy utilization and generation of contractile force by actomyosin complexes are studied. Experiments on animal models and autopsy samples showed that conformation changes precede disturbances in energy utilization by myofibrils, abnormal functioning of the energy-producing and Ca2+-transporting systems during the development of heart failure. It is proposed that rigid recombinations of submolecular structures in contracile proteins underlie impairment of myocardial contractility and resistance of the myocardium to regulatory factors and drugs (immobilization).Key Words: heart failure; conformation; energy; structure It is well known that severe heart failure can develop in the absence of macro-and microscopic pathognomic changes in the myocardium and vice versa patients with anatomically altered heart feel quite well, perform heavy physical work, live long, and die from noncardiac causes [29,101]. In the last case, morphological changes in the myocardium are completely compensated and the disease develops silently.Clinical symptoms, the degree of disability, and systolic and diastolic function of the myocardium [45,46,94] do not strictly correlate with structural and ultrastructural changes in cardiomyocytes [ 19,95] even in severe heart failure caused by congestive cardiomyopathy (CMP) and characterized by marked abnormalities in cardiomyocyte nucleus. T-tubular system, myofibrils, mitochondria (MC), and sarcoplasmic reticulum (SR) [67,118]. But all parameters are tended to decrease, which determine their coarse correlation [59. 94]. The absence of a strict correlation is probably due to nonspecific and nonpathognomic nature of morRepublican Research Center of Medical Biophysics. Ministry of Health of Georgia Republic, Tbilisi phological changes in CMP. These variances can be explained by the influence of compensatory mechanisms [34].Thus, the absence of a strict correlation (or at least its long latency) between functional activity of the heart and morphological changes in the myocardium as well as between functional states of the myocardium and subcellular structures responsible for the contraction-relaxation cycle [9,12,17,38,39] suggests that the main causes of FH lie beyond the resolution (beyond the sight) of not only light microscopy but also ultrastructural methods.It should be evaluated, what intracellular event(s) is(are) associated with reduced myocardial contractility.

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Section: Causes Of Changes In Submolecular Actomyosin Structure In Hfmentioning

confidence: 99%

Energy, structure, conformation, and heart failure

Карсанов¹

1999

Bull Exp Biol Med

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“…The strength of the interaction between TnI and TnC depends on the degree of saturation of the TnC binding sites for Ca +2 . There are multiple sites for phosphorylation of TnI, which serves an important role in regulating calcium sensitivity and actinomysin ATPase activity (Karczewski et al, 1993;Kitsis and Scheuer, 1996). A cAMP-dependent protein kinase (protein kinase A) and Ca +2 -phospholipid dependent protein kinase (protein kinase C) facilitate phosphorylation of the various TnI sites (Venema and Kuo, 1993).…”

Section: Active Sitesmentioning

confidence: 99%

Serum Troponins as Biomarkers of Drug-Induced Cardiac Toxicity

et al. 2004

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“…All these changes may probably have importance for the regulation of protein functions in heart during PDE4 inhibition. As suggested by Kitsis et al (1996) such abnormalities in these molecules, major structural and functional components of heart tissue have been postulated to be the cause of contractile dysfunction. These include fur-ther cell death and cellular dysfunctions involving contractile proteins, sarcolemma (including associated receptors and channels), sarcoplasmic reticulum and other components of the excitation-contraction coupling apparatus, mitochondria and associated anabolic proteins and various signal transductions.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of PDE4 by low doses of rolipram induces changes in lipid and protein components of mice heart

Türker-Kaya

Çelikyurt²,

Kına³

2018

gpb

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There is significant increasing interest in phosphodiesterase-4 (PDE4) inhibition in treatment of cardiovascular diseases. Related with this, research has focused on cellular, biochemical, molecular and structural changes in heart tissue induced by PDE4s inhibitors. However, for their clinical applicability additional studies are still needed. Fourier transform infrared spectroscopy offers promising approach to contribute such issue due to its ability in detection the changes in biomolecules. By utilizing this method, we examined the effects of PDE4 inhibition by rolipram at 0.05 mg/kg and 0.1 mg/kg doses on content of lipids and proteins, and fluidity, order and packing of membranes in naive mice heart. In treated groups, there was a significant decrease in unsaturated, saturated lipids, cholesterol esters, fatty acids, phospholipids and triacylgylcerols obtained from CH2, C=O, olefinic=CH, and COO- areas, and CH2/lipid, C=O/lipid, olefinic=CH/lipid, and COO-/lipid ratios. Additionally, olefinic=CH area and olefinic=CH/lipid ratio may suggest decreased lipid peroxidation, confirmed by thiobarbituric acid assay. Also, a higher degree of membrane order, slight increase in membrane fluidity and differences in membrane packing were obtained. Amide I and II areas and RNA/protein ratios showed that variation in protein content is not correlated with applied concentration. Analysis of amide I mode predicted alterations in secondary structures like an increase in random coils and decrease in alpha-helices. Moreover, all groups were successfully discriminated by cluster analysis. The corresponding results may help to understand the potential effects of PDE4 inhibition by rolipram.

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Functional significance of alterations in cardiac contractile protein isoforms

Cited by 12 publications

References 112 publications

Energy, structure, conformation, and heart failure

Energy, structure, conformation, and heart failure

Serum Troponins as Biomarkers of Drug-Induced Cardiac Toxicity

Inhibition of PDE4 by low doses of rolipram induces changes in lipid and protein components of mice heart

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