scholarly journals P2 Receptors in Cardiac Myocyte Pathophysiology and Mechanotransduction

2020 ◽  
Vol 22 (1) ◽  
pp. 251
Author(s):  
Sun-Hee Woo ◽  
Tran Nguyet Trinh
Keyword(s):  
Mammalian Cells ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Cardiac Contractility ◽  
Genetic Alterations ◽  
Cardiac Cells ◽  
Receptor Subtypes ◽  
P2 Receptor ◽  
External Application ◽  
Major Energy Source

ATP is a major energy source in the mammalian cells, but it is an extracellular chemical messenger acting on P2 purinergic receptors. A line of evidence has shown that ATP is released from many different types of cells including neurons, endothelial cells, and muscle cells. In this review, we described the distribution of P2 receptor subtypes in the cardiac cells and their physiological and pathological roles in the heart. So far, the effects of external application of ATP or its analogues, and those of UTP on cardiac contractility and rhythm have been reported. In addition, specific genetic alterations and pharmacological agonists and antagonists have been adopted to discover specific roles of P2 receptor subtypes including P2X4-, P2X7-, P2Y2- and P2Y6-receptors in cardiac cells under physiological and pathological conditions. Accumulated data suggest that P2X4 receptors may play a beneficial role in cardiac muscle function, and that P2Y2- and P2Y6-receptors can induce cardiac fibrosis. Recent evidence further demonstrates P2Y1 receptor and P2X4 receptor as important mechanical signaling molecules to alter membrane potential and Ca2+ signaling in atrial myocytes and their uneven expression profile between right and left atrium.

scholarly journals Suppressing Pyroptosis Augments Post-Transplant Survival of Stem Cells and Cardiac Function Following Ischemic Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 7946
Author(s):  
Chang Youn Lee ◽  
Seahyoung Lee ◽  
Seongtae Jeong ◽  
Jiyun Lee ◽  
Hyang-Hee Seo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion ◽  
Cardiac Cells ◽  
Transplant Survival ◽  
Post Transplant ◽  
Heart Functions ◽  
Cell Death Mechanisms

The acute demise of stem cells following transplantation significantly compromises the efficacy of stem cell-based cell therapeutics for infarcted hearts. As the stem cells transplanted into the damaged heart are readily exposed to the hostile environment, it can be assumed that the acute death of the transplanted stem cells is also inflicted by the same environmental cues that caused massive death of the host cardiac cells. Pyroptosis, a highly inflammatory form of programmed cell death, has been added to the list of important cell death mechanisms in the damaged heart. However, unlike the well-established cell death mechanisms such as necrosis or apoptosis, the exact role and significance of pyroptosis in the acute death of transplanted stem cells have not been explored in depth. In the present study, we found that M1 macrophages mediate the pyroptosis in the ischemia/reperfusion (I/R) injured hearts and identified miRNA-762 as an important regulator of interleukin 1b production and subsequent pyroptosis. Delivery of exogenous miRNA-762 prior to transplantation significantly increased the post-transplant survival of stem cells and also significantly ameliorated cardiac fibrosis and heart functions following I/R injury. Our data strongly suggest that suppressing pyroptosis can be an effective adjuvant strategy to enhance the efficacy of stem cell-based therapeutics for diseased hearts.

Species-specific Effects of Nitromethylene Heterocycle Insecticides on Nicotinic Receptors in Locust Neurons and Mouse N1E-115 and BC3H1 Cells

1994 ◽  
Vol 22 (6) ◽  
pp. 454-461
Author(s):  
Marga Oortgiesen ◽  
Ruud Zwart ◽  
Henk P.M. Vijverberg
Keyword(s):  
Mammalian Cells ◽  
Neuroblastoma Cells ◽  
Receptor Subtypes ◽  
Inward Current ◽  
Specific Effects ◽  
Blocking Effects ◽  
Inward Currents ◽  
Species Specific ◽  
Ganglion Neurons

The effects of nitromethylene heterocycle (NMH) insecticides on subtypes of nicotinic acetylcholine (nACh) receptors were investigated in locust thoracic ganglion neurons, mouse N1E-115 neuroblastoma cells, and mouse BC3H1 muscle cells by using electrophysiological techniques. In locust neurons, all of the six NMH insecticides tested induced transient inward currents resembling nicotinic ACh-induced inward currents, while, in the continued presence of the NMH compounds, the ACh-induced inward current was blocked. The amplitude of the inward current and the blocking effects of the NMH insecticides were enhanced by concentrations between 0.1 and 10μM. Cross-desensitisation with the ACh-induced inward current confirmed that the NMH-induced inward current was governed by the activation of nACh receptors. Mammalian endplate type nACh receptors in BC3H1 cells and mammalian neuronal type nACh receptors in N1E-115 cells were much less sensitive to the NMH insecticides than the locust neuronal nACh receptors. At a concentration of 10μM, which blocked 80–100% of the ACh-induced inward current in locust neurons, NMH insecticides only partially blocked the ACh-induced inward currents mediated by the two subtypes of mammalian nACh receptors. NMH insecticides also failed to induce significant agonist effects in the mammalian cells at this concentration. The results provide a possible explanation for the selectively greater toxicity of NMH insecticides to insects than to vertebrates, at the level of nACh receptor subtypes and, hence, demonstrate that this in vitro approach is valuable for the investigation of species-specific interactions of compounds at their target site.

Ouabain uptake by endocytosis in isolated guinea pig atria

1988 ◽  
Vol 255 (4) ◽  
pp. C479-C485 ◽  
Author(s):  
H. Nunez-Duran ◽  
L. Riboni ◽  
E. Ubaldo ◽  
E. Kabela ◽  
L. Barcenas-Ruiz
Keyword(s):  
Electron Microscope ◽  
Guinea Pig ◽  
Mammalian Cells ◽  
Isometric Tension ◽  
Cardiac Cells ◽  
Inotropic Effect ◽  
Experimental Protocols ◽  
Guinea Pig Atrium ◽  
Endocytic Vesicles ◽  
Guinea Pig Atria

Mammalian cells specifically internalize some molecular species through receptor-mediated endocytosis (RME). We have used four different experimental protocols to investigate whether ouabain enters cardiac cells of guinea pig atrium through this pathway. First, by electron microscope morphometry we found that ouabain increased endocytic vesicles in atrial cells. Second, by scintillation counting we found that [3H]ouabain uptake by the tissue is decreased by three treatments that decrease RME, i.e., NH4Cl, trifluoperazine, and 16 mM [K+]0. Third, by radioautography at the electron microscope level, we checked that in preceding experiments [3H]ouabain was washed out of plasma membrane after 60-min rinse and interiorized into the cardiac cells. Fourth, isometric tension recordings showed that the positive inotropic effect of ouabain was diminished in the presence of inhibitors, whereas that of a hydrophobic analogue, ouabagenin, was not affected. These results suggest that ouabain enters cardiac cells through RME and also that an intracellular site may, at least in part, be responsible for its inotropic effect.

scholarly journals Deletion of Osteopontin Enhances b2-Adrenergic Receptor-Dependent Anti-Fibrotic Signaling in Cardiomyocytes

2019 ◽  
Author(s):  
Celina M. Pollard ◽  
Victoria L. Desimine ◽  
Shelby L. Wertz ◽  
Arianna Perez ◽  
Barbara M. Parker ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Adenosine Monophosphate ◽  
Cardiac Cells ◽  
Protein Levels ◽  
Camp Generation ◽  
H9c2 Cardiomyocytes ◽  
Adverse Remodeling ◽  
Cardiac Myoblasts

Cardiac β2-adrenergic receptors (ARs) are known to inhibit collagen production and fibrosis in cardiac fibroblasts and myocytes. The β2AR is a Gs protein-coupled receptor (GPCR) and, upon its activation, stimulates generation of cyclic 3', 5'-adenosine monophosphate (cAMP). cAMP has two effectors: protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac). Epac1 has been shown to inhibit cardiac fibroblast activation and fibrosis. Osteopontin (OPN) is a ubiquitous pro-inflammatory cytokine, mediating also fibrosis in several tissues, including the heart. OPN underlies several cardiovascular pathologies, including atherosclerosis and cardiac adverse remodeling. We have found that the cardiotoxic hormone aldosterone transcriptionally upregulates OPN in H9c2 rat cardiac myoblasts, an effect prevented by endogenous β2AR activation. Additionally, CRISPR-mediated OPN deletion enhances cAMP generation in response to both b1AR and β2AR activation in H9c2 cardiomyocytes, leading to upregulation of Epac1 protein levels. These effects render β2AR stimulation capable of completely abrogating transforming growth factor (TGF)-β-dependent fibrosis in OPN-lacking H9c2 cardiomyocytes. Finally, OPN interacts constitutively with Gas subunits in H9c2 cardiac cells. Thus, we have uncovered a direct inhibitory role of OPN in cardiac β2AR anti-fibrotic signaling via cAMP/Epac1. OPN blockade could be of value in the treatment and/or prevention of cardiac fibrosis.

Compensation for partial lipectomy in mice with genetic alterations of leptin and its receptor subtypes

2002 ◽  
Vol 283 (5) ◽  
pp. R1094-R1103 ◽  
Author(s):  
Ruth B. S. Harris ◽  
Dorothy B. Hausman ◽  
Timothy J. Bartness
Keyword(s):  
Body Fat ◽  
Short Form ◽  
Genetic Alterations ◽  
Cell Number ◽  
Feedback Signal ◽  
Receptor Subtypes ◽  
Wild Type ◽  
Leptin Receptors ◽  
Total Body Fat ◽  
Total Body

One hypothesis for the regulation of total body fat suggests that leptin is a lipostatic feedback signal that acts at brain sites involved in regulation of energy balance. The importance of leptin in recovery from partial surgical lipectomy was tested by performing bilateral epididymal lipectomy or sham surgery on wild-type and leptin-deficient ob/ob mice. Eight weeks later, nonexcised pads of lipectomized mice were increased but total carcass fat was lower than in sham-operated ob/ob mice. In experiment 2, ob/ob mice, wild-type mice, and two db/db mutants, C57BL/6J dbLepr/dbLepr (BL/6J) mice possessing short-form and circulating leptin receptors and C57BL/6J db3J/db3J (BL/3J) mice expressing only circulating receptors, were lipectomized or sham operated. Sixteen weeks later, body mass and carcass lipid were not different between sham and lipectomized ob/ob mice, wild-type mice, or BL/6J db/db mice, whereas there was incomplete (decreased carcass fat) but suggestive recovery (increased retroperitoneal fat mass and cell number) in lipectomized BL/3J db/db mice. These data indicate that leptin is not required for the regulation of total body fat.

RIC-3 Enhances Functional Expression of Multiple Nicotinic Acetylcholine Receptor Subtypes in Mammalian Cells

2005 ◽  
Vol 68 (5) ◽  
pp. 1431-1438 ◽  
Author(s):  
Stuart J. Lansdell ◽  
Veronica J. Gee ◽  
Patricia C. Harkness ◽  
Anne I. Doward ◽  
Elizabeth R. Baker ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Mammalian Cells ◽  
Functional Expression ◽  
Receptor Subtypes ◽  
Nicotinic Acetylcholine

Novel role for cardiac myocyte-derived β-2 microglobulin in mediating cardiac fibrosis

2018 ◽  
Vol 132 (19) ◽  
pp. 2117-2120
Author(s):  
Michael J. Boyer ◽  
Satoru Eguchi
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Cardiac Fibroblasts ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Pressure Overload ◽  
Significant Risk Factor ◽  
Cardiac Complications

Hypertension is a significant risk factor for the development of cardiovascular ailments, including ischemic heart disease and diastolic dysfunction. In a recent issue of Clinical Science, Li et al. [Clin. Sci. (2018) 132, 1855–1874] report that β-2 microglobulin (β2M) is a novel secreted soluble factor released by cardiac myocytes during pressure overload that promotes profibrotic gene expression in cardiac fibroblasts both in vitro and in vivo. Their study further identifies elevated β2M levels as a possible biomarker for hypertensive patients with cardiac complications. The authors propose a mechanism that mechanically stretched cardiomyocytes release soluble β2M which, through paracrine communication with cardiac fibroblasts, transactivates epidermal growth factor receptor (EGFR) to initiate acute signal transduction and up-regulate profibrotic genes, thereby promoting fibrosis. Here, we will discuss the background, significance of the study, alternative mechanisms, and future directions.

Actomyosin interaction modulates resting length of unstimulated cardiac ventricular cells

1996 ◽  
Vol 271 (3) ◽  
pp. H896-H905 ◽  
Author(s):  
S. J. Sollott ◽  
B. D. Ziman ◽  
D. M. Warshaw ◽  
H. A. Spurgeon ◽  
E. G. Lakatta
Keyword(s):  
Cardiac Myocyte ◽  
Striated Muscle ◽  
Potent Inhibitor ◽  
Force Production ◽  
Cardiac Cells ◽  
Regulatory Proteins ◽  
Resting Cell ◽  
Ventricular Cells ◽  
Actomyosin Interaction ◽  
Butanedione Monoxime

We sought to determine whether resting or diastolic cardiac myocyte length during low stimulation rates is regulated by myofilament interaction. Cytosolic Ca2+ concentration ([Ca2+]i, via indo 1 fluorescence) and length, in the presence and absence of 2,3-butanedione monoxime (BDM), a potent inhibitor of force production in striated muscle, were measured in rat and guinea pig cardiac myocytes at rest and after electrical stimulation. In tetanized cells BDM reduced steady contraction amplitudes for a given [Ca2+]i. In an actomyosin-sliding filament assay without Ca2+ or regulatory proteins, BDM decreased actin filament velocity along myosin. BDM increased both diastolic and resting cell lengths without changes in [Ca2+]i. The resting cell length also increased when [Ca2+]i was reduced by removing extracellular Ca2+, an effect further enhanced by BDM and by loading cells with the intracellular Ca2+ chelator, 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethylester. Thus myofilament interaction is present in cardiac cells, both at rest or during low rates of stimulation, and this myofilament interaction is regulated, in part, by the ambient [Ca2+]i.

scholarly journals Cellular Physiology of Rat Cardiac Myocytes in Cardiac Fibrosis: In Vitro Simulation Using the Cardiac Myocyte/Cardiac Non-Myocyte Co-Culture System

2008 ◽  
Vol 31 (4) ◽  
pp. 693-706 ◽  
Author(s):  
Keiichi Ikeda ◽  
Katsuyoshi Tojo ◽  
Takashi Udagawa ◽  
Chikara Otsubo ◽  
Masahiro Ishikawa ◽  
...  
Keyword(s):  
Cardiac Myocytes ◽  
Culture System ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Cellular Physiology ◽  
In Vitro Simulation ◽  
Rat Cardiac Myocytes
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