scholarly journals Impact of circadian time of dosing on cardiac-autonomous effects of glucocorticoids

2021 ◽  
Author(s):  
Michelle Wintzinger ◽  
Manoj Panta ◽  
Karen Miz ◽  
Ashok D.P. Pragasam ◽  
Michelle Sargent ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Demand ◽  
Heart Function ◽  
Daily Intake ◽  
Metabolic Stress ◽  
Single Pulse ◽  
High Energy ◽  
Dark Phase ◽  
Light Phase ◽  
Circadian Time

Bioenergetic capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates cardiac bioenergetics through the primary receptor of these drugs, the glucocorticoid receptor (GR). While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism and heart function in dystrophic mice. However, the effects of glucocorticoid intermittence on heart failure beyond muscular dystrophy remain unknown. Here we investigated the extent to which circadian time of dosing regulates the cardiac-autonomous effects of the glucocorticoid prednisone in conditions of single pulse or chronic intermittent dosing. In WT mice, we found that prednisone improved cardiac content of NAD+ and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted GR ablation, and depended on an intact activating clock complex, as shown by hearts from BMAL1-KO mice. Conjugating time-of-dosing with chronic intermittence, we found that once-weekly light-phase prednisone improved metabolism and function in heart after myocardial injury. Our study identifies cardiac-autonomous mechanisms through which circadian time and chronic intermittence reconvert glucocorticoid drugs to bioenergetic boosters for the heart.

scholarly journals Emerging Role of Mitophagy in the Heart: Therapeutic Potentials to Modulate Mitophagy in Cardiac Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yi Luan ◽  
Ying Luan ◽  
Qi Feng ◽  
Xing Chen ◽  
Kai-Di Ren ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Supply ◽  
Heart Function ◽  
High Energy ◽  
Normal Function ◽  
Cardiac Diseases ◽  
Normal Heart ◽  
Beneficial Effects ◽  
Physiological Processes

The normal function of the mitochondria is crucial for most tissues especially for those that demand a high energy supply. Emerging evidence has pointed out that healthy mitochondrial function is closely associated with normal heart function. When these processes fail to repair the damaged mitochondria, cells initiate a removal process referred to as mitophagy to clear away defective mitochondria. In cardiomyocytes, mitophagy is closely associated with metabolic activity, cell differentiation, apoptosis, and other physiological processes involved in major phenotypic alterations. Mitophagy alterations may contribute to detrimental or beneficial effects in a multitude of cardiac diseases, indicating potential clinical insights after a close understanding of the mechanisms. Here, we discuss the current opinions of mitophagy in the progression of cardiac diseases, such as ischemic heart disease, diabetic cardiomyopathy, cardiac hypertrophy, heart failure, and arrhythmia, and focus on the key molecules and related pathways involved in the regulation of mitophagy. We also discuss recently reported approaches targeting mitophagy in the therapy of cardiac diseases.

scholarly journals Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics

2013 ◽  
Vol 41 (1) ◽  
pp. 127-133 ◽  
Author(s):  
Tanecia Mitchell ◽  
Balu Chacko ◽  
Scott W. Ballinger ◽  
Shannon M. Bailey ◽  
Jianhua Zhang ◽  
...  
Keyword(s):  
Quality Control ◽  
Energy Demand ◽  
Cell Signalling ◽  
Metabolic Stress ◽  
Short Review ◽  
High Energy ◽  
Experimental Models ◽  
Signalling Pathways ◽  
Mitochondrial Quality Control ◽  
Nitrative Stress

Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic stress, such as Type II diabetes and non-alcoholic and alcoholic steatosis, the mitochondria are subjected to multiple ‘hits’ such as hypoxia and oxidative and nitrative stress, which can overwhelm the mitochondrial quality control pathways. In addition, the underlying mitochondrial genetics that evolved to accommodate high-energy demand, low-calorie supply environments may now be maladapted to modern lifestyles (low-energy demand, high-calorie environments). The pro-oxidant and pro-inflammatory environment of a sedentary western lifestyle has been associated with modified redox cell signalling pathways such as steatosis, hypoxic signalling, inflammation and fibrosis. These data suggest that loss of mitochondrial quality control is intimately associated with the aberrant activation of redox cell signalling pathways under pathological conditions. In the present short review, we discuss evidence from alcoholic liver disease supporting this concept, the insights obtained from experimental models and the application of bioenergetic-based therapeutics in the context of maintaining mitochondrial quality.

scholarly journals Stress-induced glucocorticoids alter the rhythmic activity of Leydig cells depending on the circadian time

2021 ◽  
Author(s):  
Marija Lj Medar ◽  
Silvana A Andric ◽  
Tatjana S Kostic
Keyword(s):  
Leydig Cells ◽  
Glucocorticoid Receptors ◽  
Rhythmic Activity ◽  
Circadian System ◽  
Transcriptional Analysis ◽  
Dark Phase ◽  
Similar Response ◽  
Light Phase ◽  
Mediated Communication ◽  
Circadian Time

AbstractThe connection between two fundamental processes in cells, the stress response and circadian timekeeping, were analyzed on Leydig cells from stressed rats. Stress increased glucocorticoids and decreased testosterone blood level. Transcriptional analysis revealed different sensitivity to stress events depending on the circadian time: the majority of steroidogenesis-related genes (Lhcgr, Nr3c1, Cyp11a1, Cyp17a1, Hsd3b1/2) were down-regulated by stress in the inactive (light) phase, but in the active (dark) phase of the day, they were unchanged or even up-regulated. Stress potentiates the expression of clock elements Bmal1/BMAL1, Per1/2/PER1 and Rev-erba. Glucocorticoid-treated rats showed a similar response, likewise stress on the negative clock regulators (Rev-erba/b, Cry1/2, Per1/2), suggesting that stress-induced glucocorticoids regulate clock loops but also outside genes through E-/RORE-box. Blockade of intratesticular glucocorticoid receptors prevented stress-induced change in expression negative clock regulators. The results reveal glucocorticoid-mediated communication between the stress- and circadian-system resets the Leydig cell’s clock.

scholarly journals Human Health Risks Surveillance of Polychlorinated Biphenyls in Bovine Milk from Alluvial Plain of Punjab, Pakistan

2021 ◽  
Author(s):  
Saman Sana ◽  
Abdul Qadir ◽  
Neil P Evans ◽  
Mehvish Mumtaz ◽  
Ambreena Javaid ◽  
...  
Keyword(s):  
Polychlorinated Biphenyls ◽  
Energy Demand ◽  
Research Work ◽  
Daily Intake ◽  
Bovine Milk ◽  
Dietary Exposure ◽  
High Energy ◽  
Average Concentration ◽  
Cow Milk ◽  
Milk Samples

Abstract Punjab is the leading province of Pakistan in the production of bovine milk and its consumption. Rapid industrialization, high energy demand and production of waste have increased the risk of PCB toxicity in the environment. This research work was designed to assess human dietary exposure of polychlorinated biphenyls (∑PCBs 17 congeners) through ingestion of buffalo and cow’s milk from eight main districts of Punjab, Pakistan. The average concentration of ∑DL-PCBs in buffalo and cow milk samples were analyzed (8.74 ng g-1 and 14.60 ng g-1) and ∑I-PCBs (11.54 ng g-1 and 18.68 ng g-1) respectively. The PCB-156 was predominantly high congener found in both buffalo (2.84 ng g-1) and cow milk (2.86 ng g-1). It was found that the highest PCBs in bovine milk samples were observed in close vicinities of urban and industrial areas. The estimated daily consumptions of DL-PCBs and I-PCBs, from buffalo and cow milk, were below the acceptable daily intake for both adults and children. Moreover, Hazard Quotients (HQ) of ∑PCBs17 congeners value were less than 1.0 in adults and greater in the case of children reflecting the high chances of cancer risk. Furthermore, comprehensive monitoring for childhood cancer is recommended to establish the relationship in future studies.

Energy metabolism in patients with diabetes and heart failure

2019 ◽  
pp. 32-36
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Oxidative Phosphorylation ◽  
Energy Demand ◽  
Glucose Oxidation ◽  
High Energy ◽  
Energy Deficit ◽  
Diabetic Patients ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Myocardial Energy Metabolism

The heart has a very high energy demand, which is mostly met by mitochondrial oxidative phosphorylation and, to a lesser extent, by glycolysis. In heart failure, there are substantial alterations in myocardial energy metabolism that lead to an “energy-deficient” state. This includes a marked reduction in overall mitochondrial oxidative phosphorylation and an uncoupling between high glycolysis rates and low glucose oxidation, which together contributes to the energy deficit and deteriorates contractile dysfunction. Cardiac ketone oxidation is also increased in heart failure, although it has yet to be determined whether this is an adaptive or maladaptive alteration. Diabetes is a major risk factor for heart failure development. It induces alterations in myocardial energy metabolism and is often associated with ventricular dysfunction. Similar to heart failure, a major change in myocardial energy metabolism in diabetic patients is a reduction in glucose oxidation, which negatively influences cardiac function. In both heart failure and diabetes, a growing body of evidence suggests that targeting myocardial energy metabolism by optimizing cardiac energy substrate preference could be a potential therapeutic approach to improve patient outcomes.

Changes in lipid peroxidation during pregnancy and after delivery in rats: effect of pinealectomy

Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Oxidative Damage ◽  
Energy Demand ◽  
Physiological State ◽  
High Energy ◽  
Free Radical Scavengers ◽  
Radical Scavengers ◽  
Oxygen Requirement ◽  
Pregnant Rats

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.

scholarly journals Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Dark Phase ◽  
Light Phase ◽  
Dark Cycle ◽  
Simultaneous Activation ◽  
Type 3 ◽  
G Protein Coupled

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

scholarly journals Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Implantable Pulse Generator ◽  
Defibrillation Pulse ◽  
Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

scholarly journals The Quorum Sensing Auto-Inducer 2 (AI-2) Stimulates Nitrogen Fixation and Favors Ethanol Production over Biomass Accumulation in Zymomonas mobilis

2021 ◽  
Vol 22 (11) ◽  
pp. 5628
Author(s):  
Valquíria Campos Alencar ◽  
Juliana de Fátima dos Santos Silva ◽  
Renata Ozelami Vilas Boas ◽  
Vinícius Manganaro Farnézio ◽  
Yara N. L. F. de Maria ◽  
...  
Keyword(s):  
Nitrogen Fixation ◽  
Quorum Sensing ◽  
Ethanol Production ◽  
N2 Fixation ◽  
Energy Demand ◽  
Zymomonas Mobilis ◽  
Biomass Accumulation ◽  
High Energy ◽  
Gram Negative ◽  
Expression Of Genes

Autoinducer 2 (or AI-2) is one of the molecules used by bacteria to trigger the Quorum Sensing (QS) response, which activates expression of genes involved in a series of alternative mechanisms, when cells reach high population densities (including bioluminescence, motility, biofilm formation, stress resistance, and production of public goods, or pathogenicity factors, among others). Contrary to most autoinducers, AI-2 can induce QS responses in both Gram-negative and Gram-positive bacteria, and has been suggested to constitute a trans-specific system of bacterial communication, capable of affecting even bacteria that cannot produce this autoinducer. In this work, we demonstrate that the ethanologenic Gram-negative bacterium Zymomonas mobilis (a non-AI-2 producer) responds to exogenous AI-2 by modulating expression of genes involved in mechanisms typically associated with QS in other bacteria, such as motility, DNA repair, and nitrogen fixation. Interestingly, the metabolism of AI-2-induced Z. mobilis cells seems to favor ethanol production over biomass accumulation, probably as an adaptation to the high-energy demand of N2 fixation. This opens the possibility of employing AI-2 during the industrial production of second-generation ethanol, as a way to boost N2 fixation by these bacteria, which could reduce costs associated with the use of nitrogen-based fertilizers, without compromising ethanol production in industrial plants.

scholarly journals IoT Platform for Energy Sustainability in University Campuses

Sensors ◽  
2021 ◽  
Vol 21 (2) ◽  
pp. 357
Author(s):  
Pedro Moura ◽  
José Ignacio Moreno ◽  
Gregorio López López ◽  
Manuel Alvarez-Campana
Keyword(s):  
Energy Demand ◽  
New Technologies ◽  
Low Cost ◽  
Sustainable Use ◽  
High Energy ◽  
Appropriate Technology ◽  
Monitoring And Control ◽  
Energy Sustainability ◽  
University Campuses ◽  
Iot Platform

University campuses are normally constituted of large buildings responsible for high energy demand, and are also important as demonstration sites for new technologies and systems. This paper presents the results of achieving energy sustainability in a testbed composed of a set of four buildings that constitute the Telecommunications Engineering School of the Universidad Politécnica de Madrid. In the paper, after characterizing the consumption of university buildings for a complete year, different options to achieve more sustainable use of energy are presented, considering the integration of renewable generation sources, namely photovoltaic generation, and monitoring and controlling electricity demand. To ensure the implementation of the desired monitoring and control, an internet of things (IoT) platform based on wireless sensor network (WSN) infrastructure was designed and installed. Such a platform supports a smart system to control the heating, ventilation, and air conditioning (HVAC) and lighting systems in buildings. Furthermore, the paper presents the developed IoT-based platform, as well as the implemented services. As a result, the paper illustrates how providing old existing buildings with the appropriate technology can contribute to the objective of transforming such buildings into nearly zero-energy buildings (nZEB) at a low cost.

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