Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

Obesity is associated with aberrant sodium/potassium-ATPase (Na+/K+-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na+/K+-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na+/K+-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na+/K+-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na+/K+-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na+/K+-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na+/K+-ATPase activity.

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Antioxidants in Sport Sarcopenia

Nutrients ◽

10.3390/nu12092869 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2869

Author(s):

Maria Michela Cesare ◽

Francesca Felice ◽

Veronica Santini ◽

Rossella Di Stefano

Keyword(s):

Muscle Mass ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

Physiological State ◽

Experimental Models ◽

Adaptive Responses ◽

Master Athletes ◽

Intracellular Signaling Pathways ◽

Endogenous Protection ◽

New Strategies

The decline of skeletal muscle mass and strength that leads to sarcopenia is a pathology that might represent an emergency healthcare issue in future years. Decreased muscle mass is also a condition that mainly affects master athletes involved in endurance physical activities. Skeletal muscles respond to exercise by reshaping the biochemical, morphological, and physiological state of myofibrils. Adaptive responses involve the activation of intracellular signaling pathways and genetic reprogramming, causing alterations in contractile properties, metabolic status, and muscle mass. One of the mechanisms leading to sarcopenia is an increase in reactive oxygen and nitrogen species levels and a reduction in enzymatic antioxidant protection. The present review shows the recent experimental models of sarcopenia that explore molecular mechanisms. Furthermore, the clinical aspect of sport sarcopenia will be highlighted, and new strategies based on nutritional supplements, which may contribute to reducing indices of oxidative stress by reinforcing natural endogenous protection, will be suggested.

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Localization of Adenosine Triphosphatase Activity in the Phleom of Nicotiana Tabacum

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100094401 ◽

1972 ◽

Vol 30 ◽

pp. 230-231

Author(s):

James Cronshaw ◽

Jamison E. Gilder

Keyword(s):

Plasma Membrane ◽

Atpase Activity ◽

Adenosine Triphosphatase ◽

Higher Plants ◽

High Surface ◽

Root Tip ◽

Animal Cells ◽

Physiological Processes ◽

Tip Cells ◽

Atpase Localization

Adenosine triphosphatase (ATPase) activity has been shown to be associated with numerous physiological processes in both plants and animal cells. Biochemical studies have shown that in higher plants ATPase activity is high in cell wall preparations and is associated with the plasma membrane, nuclei, mitochondria, chloroplasts and lysosomes. However, there have been only a few ATPase localization studies of higher plants at the electron microscope level. Poux (1967) demonstrated ATPase activity associated with most cellular organelles in the protoderm cells of Cucumis roots. Hall (1971) has demonstrated ATPase activity in root tip cells of Zea mays. There was high surface activity largely associated with the plasma membrane and plasmodesmata. ATPase activity was also demonstrated in mitochondria, dictyosomes, endoplasmic reticulum and plastids.

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Adenosine Receptor Modulation of Hypoxic-ischemic Injury in Striatum of Newborn Piglets

Current Neurovascular Research ◽

10.2174/1567202617999200831152233 ◽

2020 ◽

Vol 17 (4) ◽

pp. 510-517

Author(s):

Santiago Ortega-Gutierrez ◽

Brandy Jones ◽

Alan Mendez-Ruiz ◽

Pankhil Shah ◽

Michel T. Torbey

Keyword(s):

Oxidative Stress ◽

Atpase Activity ◽

Neuronal Injury ◽

Receptor Activation ◽

Adult Mortality ◽

Vehicle Group ◽

Sodium Potassium ◽

Receptor Modulation ◽

A2a Receptor ◽

Potassium Atpase

Background: Hypoxic-ischemic encephalopathy (HIE) is a major cause of pediatric and adult mortality and morbidity. Unfortunately, to date, no effective treatment has been identified. In the striatum, neuronal injury is analogous to the cellular mechanism of necrosis observed during NMethyl- D-Aspartate (NMDA) excitotoxicity. Adenosine acts as a neuromodulator in the central nervous system, the role of which relies mostly on controlling excitatory glutamatergic synapses. Objective: To examine the effect of pretreatment of SCH58261, an adenosine 2A (A2A) receptor antagonist and modulator of NMDA receptor function, following hypoxic-ischemia (HI) on sodium- potassium ATPase (Na+, K+-ATPase) activity and oxidative stress. Methods: Piglets (4-7 days old) were subjected to 30 min hypoxia and 7 min of airway occlusion producing asphyxic cardiac arrest. Groups were divided into four categories: HI samples were divided into HI-vehicle group (n = 5) and HI-A2A group (n = 5). Sham controls were divided into Sham vehicle (n = 5) and Sham A2A (n = 5) groups. Vehicle groups were pretreated with 0.9% saline, whereas A2A animals were pretreated with SCH58261 10 min prior to intervention. Striatum samples were collected 3 h post-arrest. Sodium-potassium ATPase (Na+, K+-ATPase) activity, malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) and glutathione (GSH) levels were compared. Results: Pretreatment with SCH58261 significantly attenuated the decrease in Na+, K+-ATPase, decreased MDA+4-HDA levels and increased GSH in the HI-A2A group when compared to HIvehicle. Conclusion: A2A receptor activation may contribute to neuronal injury in newborn striatum after HI in association with decreased Na+, K+-ATPase activity and increased oxidative stress.

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Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

Current Cancer Drug Targets ◽

10.2174/1568009618666180102103959 ◽

2018 ◽

Vol 18 (10) ◽

pp. 967-978 ◽

Cited By ~ 8

Author(s):

Katarina Kalavska ◽

Vincenza Conteduca ◽

Ugo De Giorgi ◽

Michal Mego

Keyword(s):

Germ Cell ◽

Molecular Mechanisms ◽

Cisplatin Resistance ◽

Apoptotic Cell ◽

Germ Cell Tumors ◽

Treatment Resistance ◽

Experimental Models ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

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Renal sodium-potassium adenosine triphosphatase. Optical localization and x-ray microanalysis.

Journal of Histochemistry & Cytochemistry ◽

10.1177/23.11.127810 ◽

1975 ◽

Vol 23 (11) ◽

pp. 828-839 ◽

Cited By ~ 28

Author(s):

R Beeuwkes ◽

S Rosen

Keyword(s):

Atpase Activity ◽

Electron Probe ◽

Sequential Analysis ◽

Relative Sensitivity ◽

Initial Reaction ◽

Initial Product ◽

Sodium Potassium ◽

Nitrophenyl Phosphate ◽

Hydrolysis Of ◽

Convoluted Tubules

The distribution of sodium-potassium adenosine triposphatase (Na-K-ATPase) activity in kidney sections has been studied by a method based on the hydrolysis of p-nitrophenyl phosphate in alkaline medium containing dimethyl sulfoxide. The products at each stage in the reaction sequence have been subjected to electron probe microanalysis. The initial product was identified as a mixture of KMgPO4 and Mg(PO4)2, and sequential analysis demonstrated the linearity of conversion of this product to a visible form. In human, rabbit and rat kidneys the distribution of activity was found to be essentially identical, with highest levels located in thick ascending limbs and distal convoluted tubules. The initial reaction was completely potassium dependent and was inhibited by ouabain in concentrations reflecting the relative sensitivity of microsomal Na-K-ATPase in each species. Measurement of initial product phosphorus by means of the electron probe is presented as a practical technique for direct quantitation of Na-K-ATPase activity in identified tubule segments.

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Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms22020751 ◽

2021 ◽

Vol 22 (2) ◽

pp. 751

Author(s):

Min Young Park ◽

Bala Murali Krishna Vasamsetti ◽

Wan Seop Kim ◽

Hee Jung Kang ◽

Do-Young Kim ◽

...

Keyword(s):

Graft Rejection ◽

Molecular Mechanisms ◽

Cardiac Fibrosis ◽

Cardiac Tissue ◽

Inflammatory Responses ◽

Blood Parameters ◽

Quantitative Real Time Pcr ◽

Porcine Heart ◽

End Stage Heart Failure ◽

End Stage

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.

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The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

International Journal of Molecular Sciences ◽

10.3390/ijms22158338 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8338

Author(s):

Asad Jan ◽

Nádia Pereira Gonçalves ◽

Christian Bjerggaard Vaegter ◽

Poul Henning Jensen ◽

Nelson Ferreira

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Mechanisms ◽

De Novo ◽

Alpha Synuclein ◽

Experimental Models ◽

Cellular Factors ◽

Recent Developments ◽

Novel Targets ◽

Presynaptic Protein

The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.

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Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽

10.3390/cancers13153651 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3651

Author(s):

Alexandru Blidisel ◽

Iasmina Marcovici ◽

Dorina Coricovac ◽

Florin Hut ◽

Cristina Adriana Dehelean ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Molecular Mechanisms ◽

Prediction Models ◽

3D Models ◽

Experimental Models ◽

Health Concern ◽

Liver Carcinoma ◽

Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

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Endurance Training Regulates Expression of Some Angiogenesis-Related Genes in Cardiac Tissue of Experimentally Induced Diabetic Rats

Biomolecules ◽

10.3390/biom11040498 ◽

2021 ◽

Vol 11 (4) ◽

pp. 498

Author(s):

Mojdeh Khajehlandi ◽

Lotfali Bolboli ◽

Marefat Siahkuhian ◽

Mohammad Rami ◽

Mohammadreza Tabandeh ◽

...

Keyword(s):

Gene Expression ◽

Endurance Training ◽

Molecular Mechanisms ◽

Cardiac Tissue ◽

Critical Role ◽

Diabetic Rats ◽

Moderate Intensity ◽

Pcr Analysis ◽

Cardiac Tissues ◽

The Impact

Exercise can ameliorate cardiovascular dysfunctions in the diabetes condition, but its precise molecular mechanisms have not been entirely understood. The aim of the present study was to determine the impact of endurance training on expression of angiogenesis-related genes in cardiac tissue of diabetic rats. Thirty adults male Wistar rats were randomly divided into three groups (N = 10) including diabetic training (DT), sedentary diabetes (SD), and sedentary healthy (SH), in which diabetes was induced by a single dose of streptozotocin (50 mg/kg). Endurance training (ET) with moderate-intensity was performed on a motorized treadmill for six weeks. Training duration and treadmill speed were increased during five weeks, but they were kept constant at the final week, and slope was zero at all stages. Real-time polymerase chain reaction (RT-PCR) analysis was used to measure the expression of myocyte enhancer factor-2C (MEF2C), histone deacetylase-4 (HDAC4) and Calmodulin-dependent protein kinase II (CaMKII) in cardiac tissues of the rats. Our results demonstrated that six weeks of ET increased gene expression of MEF2C significantly (p < 0.05), and caused a significant reduction in HDAC4 and CaMKII gene expression in the DT rats compared to the SD rats (p < 0.05). We concluded that moderate-intensity ET could play a critical role in ameliorating cardiovascular dysfunction in a diabetes condition by regulating the expression of some angiogenesis-related genes in cardiac tissues.

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Molecular Responses during Plant Grafting and Its Regulation by Auxins, Cytokinins, and Gibberellins

Biomolecules ◽

10.3390/biom9090397 ◽

2019 ◽

Vol 9 (9) ◽

pp. 397 ◽

Cited By ~ 4

Author(s):

Anket Sharma ◽

Bingsong Zheng

Keyword(s):

Plant Hormones ◽

Growth And Development ◽

Molecular Mechanisms ◽

Main Process ◽

Graft Union ◽

Physiological Processes ◽

Current Review ◽

Postharvest Life ◽

Successful Production

Plant grafting is an important horticulture technique used to produce a new plant after joining rootstock and scion. This is one of the most used techniques by horticulturists to enhance the quality and production of various crops. Grafting helps in improving the health of plants, their yield, and the quality of plant products, along with the enhancement of their postharvest life. The main process responsible for successful production of grafted plants is the connection of vascular tissues. This step determines the success rate of grafts and hence needs to be studied in detail. There are many factors that regulate the connection of scion and stock, and plant hormones are of special interest for researchers in the recent times. These phytohormones act as signaling molecules and have the capability of translocation across the graft union. Plant hormones, mainly auxins, cytokinins, and gibberellins, play a major role in the regulation of various key physiological processes occurring at the grafting site. In the current review, we discuss the molecular mechanisms of graft development and the phytohormone-mediated regulation of the growth and development of graft union.

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