scholarly journals The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

2022 ◽  
Vol 2022 ◽  
pp. 1-33
Author(s):  
Michele Bevere ◽  
Caterina Morabito ◽  
Maria A. Mariggiò ◽  
Simone Guarnieri
Keyword(s):  
Energy Demand ◽  
Structural Organization ◽  
Cardiac Tissue ◽  
Protein Complexes ◽  
Structural Proteins ◽  
Oxidative Balance ◽  
Pathological Conditions ◽  
Cardiac Functions ◽  
Intracellular Ros ◽  
Cell Components

This review is aimed at providing an overview of the key hallmarks of cardiomyocytes in physiological and pathological conditions. The main feature of cardiac tissue is the force generation through contraction. This process requires a conspicuous energy demand and therefore an active metabolism. The cardiac tissue is rich of mitochondria, the powerhouses in cells. These organelles, producing ATP, are also the main sources of ROS whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases. This review highlights the metabolic aspects of cardiomyocytes and wanders through the main systems of these cells: (a) the unique structural organization (such as different protein complexes represented by contractile, regulatory, and structural proteins); (b) the homeostasis of intracellular Ca2+ that represents a crucial ion for cardiac functions and E-C coupling; and (c) the balance of Zn2+, an ion with a crucial impact on the cardiovascular system. Although each system seems to be independent and finely controlled, the contractile proteins, intracellular Ca2+ homeostasis, and intracellular Zn2+ signals are strongly linked to each other by the intracellular ROS management in a fascinating way to form a “functional tetrad” which ensures the proper functioning of the myocardium. Nevertheless, if ROS balance is not properly handled, one or more of these components could be altered resulting in deleterious effects leading to an unbalance of this “tetrad” and promoting cardiovascular diseases. In conclusion, this “functional tetrad” is proposed as a complex network that communicates continuously in the cardiomyocytes and can drive the switch from physiological to pathological conditions in the heart.

scholarly journals Cardiac Organoids to Model and Heal Heart Failure and Cardiomyopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 563
Author(s):  
Magali Seguret ◽  
Eva Vermersch ◽  
Charlène Jouve ◽  
Jean-Sébastien Hulot
Keyword(s):  
Tissue Engineering ◽  
Drug Testing ◽  
Cardiac Tissue ◽  
Cardiac Tissue Engineering ◽  
Cardiac Cells ◽  
Cardiac Functions ◽  
Different Types ◽  
Recent Developments ◽  
Human Cardiac Tissue ◽  
Key Aspects

Cardiac tissue engineering aims at creating contractile structures that can optimally reproduce the features of human cardiac tissue. These constructs are becoming valuable tools to model some of the cardiac functions, to set preclinical platforms for drug testing, or to alternatively be used as therapies for cardiac repair approaches. Most of the recent developments in cardiac tissue engineering have been made possible by important advances regarding the efficient generation of cardiac cells from pluripotent stem cells and the use of novel biomaterials and microfabrication methods. Different combinations of cells, biomaterials, scaffolds, and geometries are however possible, which results in different types of structures with gradual complexities and abilities to mimic the native cardiac tissue. Here, we intend to cover key aspects of tissue engineering applied to cardiology and the consequent development of cardiac organoids. This review presents various facets of the construction of human cardiac 3D constructs, from the choice of the components to their patterning, the final geometry of generated tissues, and the subsequent readouts and applications to model and treat cardiac diseases.

Abstract 126: Peroxisomal Proliferator Activated Receptor Alpha Overexpression in Hypertrophied Cardiomyocytes Restores Mitochondrial Integrity and Function

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Sagartirtha Sarkar ◽  
Santanu Rana
Keyword(s):  
Energy Demand ◽  
Cardiac Tissue ◽  
Structural Integrity ◽  
Heart Function ◽  
Ros Generation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Atp Production ◽  
Receptor Alpha ◽  
And Function

Cardiac tissue engineering is an interdisciplinary field that engineers modulation of viable molecular milieu to restore, maintain or improve heart function. Myocardial workload (energy demand) and energy substrate availability (supply) are in continual flux to maintain specialized cellular processes, yet the heart has a limited capacity for substrate storage and utilization during pathophysiological conditions. Damage to heart muscle, acute or chronic, leads to dysregulation of cardiac metabolic processes associated with gradual but progressive decline in mitochondrial respiratory pathways resulting in diminished ATP production. The Peroxisome Proliferator Activated Receptor Alpha ( PPARα ) is known to regulate fatty acid to glucose metabolic balance as well as mitochondrial structural integrity. In this study, a non-canonical pathway of PPARα was analyzed by cardiomyocyte targeted PPARα overexpression during cardiac hypertrophy that showed significant downregulation in p53 acetylation as well as GSK3β activation levels. Targeted PPARα overexpression during hypertrophy resulted in restoration of mitochondrial structure and function along with significantly improved mitochondrial ROS generation and membrane potential. This is the first report of myocyte targeted PPARα overexpression in hypertrophied myocardium that results in an engineered heart with significantly improved function with increased muscle mitochondrial endurance and reduced mitochondrial apoptotic load, thus conferring a greater resistance to pathological stimuli within cardiac microenvironment.

scholarly journals Intracellular reactive oxygen species as apparent modulators of heat-shock protein 27 (hsp27) structural organization and phosphorylation in basal and tumour necrosis factor α-treated T47D human carcinoma cells

1995 ◽  
Vol 312 (2) ◽  
pp. 367-375 ◽  
Author(s):  
P Mehlen ◽  
C Kretz-Remy ◽  
J Briolay ◽  
P Fostan ◽  
M E Mirault ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumour Necrosis ◽  
Structural Organization ◽  
Tnf Alpha ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Gshpx Activity ◽  
Necrosis Factor

The small stress protein heat-shock protein 27 (hsp27) is an oligomeric phosphoprotein, constitutively expressed in most human cells, which enhances cellular resistance to tumour necrosis factor alpha (TNF alpha). This phenomenon correlates with dramatic changes in hsp27 cellular location, structural organization and phosphorylation. To gain a better understanding of the molecular mechanisms regulating these properties of hsp27, we investigated whether they were a consequence of the intracellular production of reactive oxygen species (ROS) generated by TNF alpha. Here, we report that, in T47D carcinoma cell lines, the rapid burst of intracellular ROS production and changes in hsp27 locale, structural organization and phosphoisoform composition induced by TNF alpha were abolished by the overexpression of the antioxidant enzyme seleno-glutathione peroxidase (GSHPx). These effects were greatly diminished when GSHPx-expressing cells were grown in the absence of selenium, a cofactor that is essential for seleno-GSHPx activity, indicating that they are directly linked to the increased GSHPx activity. Moreover, in growing T47D cells, GSHPx expression induced intracellular redistribution of hsp27 and decreased the phosphorylation of this protein without altering its pattern of oligomerization. In contrast, the heat-mediated phosphorylation of hsp27 was not altered by decreased intracellular ROS levels. Hence, in growing and TNF-treated cells, several hsp27 properties appear to be modulated by fluctuations in intracellular ROS levels.

Abstract 517: Substrate Dependence of Mitochondrial Supercomplex Abundance in Murine Heart

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Tariq R Altamimi ◽  
Timothy N Audam ◽  
Yuting Zheng ◽  
Andrew Gibb ◽  
Siqi Liu ◽  
...  
Keyword(s):  
Energy Demand ◽  
Protein Complexes ◽  
Polyacrylamide Gel Electrophoresis ◽  
High Energy ◽  
Fatty Acyl ◽  
Dependent Manner ◽  
Substrate Dependence ◽  
Native Polyacrylamide Gel Electrophoresis ◽  
Fuel Preference

Mitochondrial supercomplexes are prominent in mammalian tissues that have high energy demand. Nevertheless, the mechanisms that regulate supercomplex formation and abundance remain unclear. In this study, we examined how myocardial fuel preference regulated by constitutive changes in phosphofructokinase (PFK) activity in vivo or by differential substrate provision to isolated mitochondria affect mitochondrial supercomplexes. Protein complexes from digitonin-solubilized cardiac mitochondria were resolved by blue-native polyacrylamide gel electrophoresis and were identified by mass spectrometry and immunoblotting to contain Complexes I, III, and IV as well as accessory proteins. Mitochondria from hearts with low PFK activity (Glyco Lo hearts) had higher mitochondrial supercomplex abundance and activity compared with mitochondria from wild-type (WT) or Glyco Hi hearts. Incubation of WT mitochondria with fatty acyl carnitine promoted higher supercomplex formation than did incubation with pyruvate, suggesting that substrate utilization is sufficient to regulate mitochondrial supercomplex abundance. These data are consistent with the hypothesis that mitochondrial supercomplex abundance is regulated in a substrate-dependent manner and suggest that metabolic scenarios favoring fat oxidation may promote supercomplex abundance.

scholarly journals Cardiac Fibroblast-Derived Extracellular Matrix (Biomatrix) as a Model for the Studies of Cardiac Primitive Cell Biological Properties in Normal and Pathological Adult Human Heart

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Clotilde Castaldo ◽  
Franca Di Meglio ◽  
Rita Miraglia ◽  
Anna Maria Sacco ◽  
Veronica Romano ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tissue Regeneration ◽  
Human Heart ◽  
Cardiac Tissue ◽  
Biological Properties ◽  
Cardiac Fibroblast ◽  
Primitive Cell ◽  
Matricellular Proteins ◽  
Adult Human ◽  
Pathological Conditions

Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM) change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease) and highlights the potential use of cardiac fibroblast-derived ECM forin vitrostudies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix), composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

scholarly journals Alterations of Golgi Structural Proteins and Glycosylation Defects in Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaoyan Zhang
Keyword(s):  
Current Knowledge ◽  
Protein Glycosylation ◽  
Structural Proteins ◽  
Pathological Conditions ◽  
Golgi Structure ◽  
Set Up ◽  
Proper Functions ◽  
And Function ◽  
Glycosylation Defect ◽  
Endocytic Pathways

As the central hub in the secretory and endocytic pathways, the Golgi apparatus continually receives the flow of cargos and serves as a major processing station in the cell. Due to its dynamic nature, a sophisticated and constantly remodeling mechanism needs to be set up to maintain the Golgi architecture and function in the non-stop trafficking of proteins and lipids. Abundant evidence has been accumulated that a well-organized Golgi structure is required for its proper functions, especially protein glycosylation. Remarkably, altered glycosylation has been a hallmark of most cancer cells. To understand the causes of Golgi defects in cancer, efforts have been made to characterize Golgi structural proteins under physiological and pathological conditions. This review summarizes the current knowledge of crucial Golgi structural proteins and their connections with tumor progression. We foresee that understanding the Golgi structural and functional defects may help solve the puzzle of whether glycosylation defect is a cause or effect of oncogenesis.

scholarly journals Phosphatidylinositol Monophosphates Regulate Optimal Vav1 Signaling Output

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1649 ◽  
Author(s):  
Sonia Rodríguez-Fdez ◽  
Carmen Citterio ◽  
L. Francisco Lorenzo-Martín ◽  
Jesús Baltanás-Copado ◽  
Clara Llorente-González ◽  
...  
Keyword(s):  
Protein Complexes ◽  
Second Messenger ◽  
Mechanisms Of Action ◽  
Synergistic Action ◽  
Pathological Conditions ◽  
C1 Domain ◽  
Intracellular Targets ◽  
Lipid Interaction ◽  
Structural Solution

Phosphatidylinositol–5 phosphate (PI5P) and other mono-phosphoinositides (mono-PIs) play second messenger roles in both physiological and pathological conditions. Despite this, their intracellular targets and mechanisms of action remain poorly characterized. Here, we show that Vav1, a protein that exhibits both Rac1 GDP/GTP exchange and adaptor activities, is positively modulated by PI5P and, possibly, other mono-PIs. Unlike other phospholipid–protein complexes, the affinity and specificity of the Vav1–lipid interaction entail a new structural solution that involves the synergistic action of the Vav1 C1 domain and an adjacent polybasic tail. This new regulatory layer, which is not conserved in the Vav family paralogs, favors the engagement of optimal Vav1 signaling outputs in lymphocytes.

scholarly journals Mass Spectrometry-Based Characterization of the Virion Proteome, Phosphoproteome, and Associated Kinase Activity of Human Cytomegalovirus

2020 ◽  
Vol 8 (6) ◽  
pp. 820
Author(s):  
Yohann Couté ◽  
Alexandra Kraut ◽  
Christine Zimmermann ◽  
Nicole Büscher ◽  
Anne-Marie Hesse ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Kinase Activity ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Cellular Proteins ◽  
Structural Proteins ◽  
Virion Protein ◽  
Host Proteins ◽  
Essential Prerequisite

The assembly of human cytomegalovirus (HCMV) virions is an orchestrated process that requires, as an essential prerequisite, the complex crosstalk between viral structural proteins. Currently, however, the mechanisms governing the successive steps in the constitution of virion protein complexes remain elusive. Protein phosphorylation is a key regulator determining the sequential changes in the conformation, binding, dynamics, and stability of proteins in the course of multiprotein assembly. In this review, we present a comprehensive map of the HCMV virion proteome, including a refined view on the virion phosphoproteome, based on previous publications supplemented by new results. Thus, a novel dataset of viral and cellular proteins contained in HCMV virions is generated, providing a basis for future analyses of individual phosphorylation steps and sites involved in the orchestrated assembly of HCMV virion-specific multiprotein complexes. Finally, we present the current knowledge on the activity of pUL97, the HCMV-encoded and virion-associated kinase, in phosphorylating viral and host proteins.

The role of heterogeneities and intercellular coupling in wave propagation in cardiac tissue

2006 ◽  
Vol 364 (1842) ◽  
pp. 1299-1311 ◽  
Author(s):  
Benjamin E Steinberg ◽  
Leon Glass ◽  
Alvin Shrier ◽  
Gil Bub
Keyword(s):  
Wave Propagation ◽  
Plane Wave ◽  
Cardiac Tissue ◽  
Dimensionless Parameter ◽  
Spiral Waves ◽  
Excitable Media ◽  
Intercellular Coupling ◽  
Pathological Conditions ◽  
Linear Decrease

Electrical heterogeneities play a role in the initiation of cardiac arrhythmias. In certain pathological conditions such as ischaemia, current sinks can develop in the diseased cardiac tissue. In this study, we investigate the effects of changing the amount of heterogeneity and intercellular coupling on wavefront stability in a cardiac cell culture system and a mathematical model of excitable media. In both systems, we observe three types of behaviour: plane wave propagation without breakup, plane wave breakup into spiral waves and plane wave block. In the theoretical model, we observe a linear decrease in propagation velocity as the number of heterogeneities is increased, followed by a rapid, nonlinear decrease to zero. The linear decrease results from the heterogeneities acting independently on the wavefront. A general scaling argument that considers the degree of system heterogeneity and the properties of the excitable medium is used to derive a dimensionless parameter that describes the interaction of the wavefront with the heterogeneities.

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