scholarly journals Exercise-activated Ca2+ entry and enhanced risk of heat stroke

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Barbara Girolami ◽  
Matteo Serano ◽  
Antonio Michelucci ◽  
Laura Pietrangelo ◽  
Feliciano Protasi
Keyword(s):  
Environmental Conditions ◽  
Prolonged Exercise ◽  
Ex Vivo ◽  
Heat Stroke ◽  
Internal Temperature ◽  
Strenuous Physical Exercise ◽  
Voluntary Running ◽  
Single Bout ◽  
Old Mice ◽  
Control Samples

Exertional/environmental heat strokes (EHSs) are hyperthermic crises triggered by strenuous physical exercise and/or exposure to environmental heat, and are caused by an altered intracellular Ca2+ homeostasis in muscle. We recently demonstrated that a single bout of exercise on treadmill leads to formation of calcium entry units (CEUs), intracellular junctions that promote interaction between STIM1 and Orai1, the two proteins that mediate store-operated Ca2+ entry (SOCE). SOCE is a mechanism that is activated during muscle fatigue and that allows for recovery of extracellular Ca2+ during prolonged activity. The hypothesis underlying this work is that assembly of CEUs during prolonged exercise may predispose to EHSs when exercise is performed in challenging environmental conditions. To test this hypothesis, 4-mo-old mice were (1) divided into three experimental groups: control, trained-1m (1 mo of voluntary running in wheel cages), and exercised-1h (1 h of incremental treadmill run); and (2) subjected to an exertional stress (ES) protocol consisting of an incremental 45-min treadmill run at 34°C and 40% humidity. We then (a) measured the internal temperature of mice, which was higher in the two pre-exercised groups (trained-1m: 38.9°C ± 0.33; exercised-1h: 38.7°C ± 0.40) compared with control animals (37.9°C ± 0.17); (b) applied an ex vivo ES protocol to isolated EDL muscles (tetanic stimulation performed at 30°C) and verified that samples from trained-1m and exercised-1h mice generated a tension significantly greater than control samples; and (c) analyzed CEUs by electron microscopy (EM) and verified that EDL muscles of trained-1m and exercised-1h mice contained a greater number of membranes elements forming CEUs. The data collected indicates that the presence of CEUs correlates with a greater increase in body temperature and could, in principle, predispose to EHS when exercise is performed in challenging environmental conditions.

Aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle

2005 ◽  
Vol 98 (4) ◽  
pp. 1562-1566 ◽  
Author(s):  
Troy A. Hornberger ◽  
R. D. Mateja ◽  
E. R. Chin ◽  
J. L. Andrews ◽  
K. A. Esser
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Ex Vivo ◽  
Mechanical Stimuli ◽  
S6 Kinase ◽  
Diminished Capacity ◽  
Ribosomal S6 Kinase ◽  
Passive Stretch ◽  
Old Mice ◽  
Dependent Mechanism

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.

scholarly journals Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

2017 ◽  
Vol 312 (4) ◽  
pp. R626-R636 ◽  
Author(s):  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Camilla L. Schwartz ◽  
Jakob G. Knudsen ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Prolonged Exercise ◽  
Hepatic Glycogen ◽  
Glucose Content ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Single Bout ◽  
Substrate Choice

The liver is essential in maintaining and regulating glucose homeostasis during prolonged exercise. IL-6 has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim of this study was to investigate the role of skeletal muscle IL-6 on hepatic glucose regulation and substrate choice during prolonged exercise. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice (age, 12–14 wk) and littermate lox/lox (Control) mice were either rested (Rest) or completed a single bout of exercise for 10, 60, or 120 min, and the liver was quickly obtained. Hepatic IL-6 mRNA was higher at 60 min of exercise, and hepatic signal transducer and activator of transcription 3 was higher at 120 min of exercise than at rest in both genotypes. Hepatic glycogen was higher in IL-6 MKO mice than control mice at rest, but decreased similarly during exercise in the two genotypes, and hepatic glucose content was lower in IL-6 MKO than control mice at 120 min of exercise. Hepatic phosphoenolpyruvate carboxykinase mRNA and protein increased in both genotypes at 120 min of exercise, whereas hepatic glucose 6 phosphatase protein remained unchanged. Furthermore, IL-6 MKO mice had higher hepatic pyruvate dehydrogenase (PDH)Ser232 and PDHSer300 phosphorylation than control mice at rest. In conclusion, hepatic gluconeogenic capacity in mice is increased during prolonged exercise independent of muscle IL-6. Furthermore, Skeletal muscle IL-6 influences hepatic substrate regulation at rest and hepatic glucose metabolism during prolonged exercise, seemingly independent of IL-6 signaling in the liver.

scholarly journals Functional Calsequestrin-1 Is Expressed in the Heart and Its Deficiency Is Causally Related to Malignant Hyperthermia-Like Arrhythmia

Circulation ◽  
2021 ◽  
Author(s):  
Zhipeng Sun ◽  
Luqi Wang ◽  
Lu Han ◽  
Yue Wang ◽  
Yuan Zhou ◽  
...  
Keyword(s):  
Heart Rate ◽  
Ventricular Tachycardia ◽  
Malignant Hyperthermia ◽  
Ex Vivo ◽  
Heat Stroke ◽  
Time Lapse ◽  
Underlying Mechanism ◽  
Neonatal Rat ◽  
Polymorphic Ventricular Tachycardia

Background: Calsequestrins (Casqs), comprising the Casq1 and Casq2 isoforms, buffer Ca 2+ and regulate its release in the sarcoplasmic reticulum (SR) of skeletal and cardiac muscle, respectively. Human inherited diseases associated with mutations in CASQ1 or CASQ2 include malignant hyperthermia/environmental heat stroke (MH/EHS) and catecholaminergic polymorphic ventricular tachycardia. However, patients with an MH/EHS event often suffer from arrhythmia for which the underlying mechanism remains unknown. Methods: Working hearts from conventional ( Casq1 -KO) and cardiac-specific ( Casq1 -CKO) Casq1 knockout mice were monitored in vivo and ex vivo by electrocardiogram and electrical mapping, respectively. MH was induced by 2% isoflurane and treated intraperitoneally with dantrolene. Time-lapse imaging was used to monitor intracellular Ca 2+ activity in isolated mouse cardiomyocytes or neonatal rat ventricular myocytes (NRVMs) with knockdown, over-expression or truncation of the Casq1 gene. Conformational change in both Casqs was determined by crosslinking Western blot analysis. Results: Like MH/EHS patients, Casq1 -KO and Casq1 -CKO mice had faster basal heart rate, and ventricular tachycardia upon exposure to 2% isoflurane, which could be relieved by dantrolene. Basal sinus tachycardia and ventricular ectopic electrical triggering also occurred in Casq1 -KO hearts ex vivo . Accordingly, the ventricular cardiomyocytes from Casq1 -CKO mice displayed dantrolene-sensitive increased Ca 2+ waves and diastole premature Ca 2+ transients/oscillations upon isoflurane. NRVMs with Casq1-knockdown had enhanced spontaneous Ca2+ sparks/transients upon isoflurane, while cells over-expressing Casq1 exhibited decreased Ca2+ sparks/transients that were absent in cells with truncation of 9 amino acids at the C-terminus of Casq1. Structural evaluation showed that most of the Casq1 protein was present as a polymer and physically interacted with RyR2 in the ventricular SR. The Casq1 isoform was also expressed in human myocardium. Mechanistically, exposure to 2% isoflurane or heating at 41ºC induced Casq1 oligomerization in mouse ventricular and skeletal muscle tissues, leading to a reduced Casq1/RyR2 interaction and increased RyR2 activity in the ventricle. Conclusions: Casq1 is expressed in the heart, where it regulates SR Ca 2+ release and heart rate. Casq1 deficiency independently causes MH/EHS-like ventricular arrhythmia by trigger-induced Casq1 oligomerization and a relief of its inhibitory effect on RyR2-mediated Ca 2+ release, thus revealing a new inherited arrhythmia and a novel mechanism for MH/EHS arrhythmogenesis.

The Effect of Single and Repeated Bouts of Prolonged Cycling on Leukocyte Redistribution, Neutrophil Degranulation, IL-6, and Plasma Stress Hormone Responses

2004 ◽  
Vol 14 (5) ◽  
pp. 501-516 ◽  
Author(s):  
Tzai-Li Li ◽  
Michael Gleeson
Keyword(s):  
Prolonged Exercise ◽  
Exercise Bout ◽  
Neutrophil Function ◽  
Stress Hormone ◽  
Glucose Levels ◽  
Single Bout ◽  
Lower Plasma Glucose ◽  
Neutrophil Degranulation ◽  
Hormone Responses ◽  
Experimental Trials

This study compared immunoendocrine responses to a single bout of prolonged cycling at different times of day and to a 2nd bout of cycling at the same intensity on the same day. In a counterbalanced design, 8 men participated in 3 experimental trials separated by at least 4 d. In the afternoon exercise-only trial, subjects cycled for 2 h at 60% VO2max starting at 14:00. In the other 2 trials, subjects performed either 2 bouts of cycling at 60% VO2max for 2 h (starting at 09:00 and 14:00) or a separate resting trial. The single bout of prolonged exercise performed in the afternoon induced a larger neutrophilia and monocy-tosis than the identical bout of morning exercise, possibly the result of reduced carbohydrate availability and the circadian rhythm in cortisol levels. The 2nd prolonged exercise bout caused greater immunoendocrine responses but lower plasma glucose levels and neutrophil function compared with the 1st bout.

scholarly journals Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

2020 ◽  
Vol 21 (10) ◽  
pp. 3631 ◽  
Author(s):  
Raffaella Boggia ◽  
Federica Turrini ◽  
Alessandra Roggeri ◽  
Guendalina Olivero ◽  
Francesca Cisani ◽  
...  
Keyword(s):  
Oral Administration ◽  
Ellagic Acid ◽  
Ex Vivo ◽  
Behavioral Skills ◽  
Aged Mice ◽  
Age Related ◽  
The Central Nervous System ◽  
The Impact ◽  
Old Mice

The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.

scholarly journals In vivo magnetic resonance imaging of orthotopic prostate cancer

BioTechniques ◽  
2020 ◽  
Vol 69 (1) ◽  
pp. 37-45
Author(s):  
Murali K Ravoori ◽  
Sheela Singh ◽  
Peiying Yang ◽  
Wei Wei ◽  
Huiqin Chen ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mechanisms Of Action ◽  
Tumor Burden ◽  
Therapeutic Interventions ◽  
Resonance Imaging ◽  
Prostate Tumors ◽  
Tumor Weight ◽  
History Of ◽  
Old Mice

Methods for imaging orthotopic prostate tumors within the prostate or small tumors with extension outside the prostate are needed to more closely model human prostate tumors, which are most commonly located within the gland or may extend just through the gland. By comparing MR sequences, we found that the T2-based Dixon ‘water only’ sequence best visualized tumors within the prostate of mouse models in both young and old mice and that tumor weight derived from this sequence correlated highly with ex vivo tumor weight (r2 = 0.98, p < 0.001, n = 12). This should aid tumor detection, margin delineation and evaluation of tumor burden to enable studies including, but not limited to, evaluating the natural history of the disease, the mechanisms of action and the efficacy of therapeutic interventions.

scholarly journals TEMPERATURE CHARACTERISTICS FOR FREQUENCY OF RESPIRATORY MOVEMENTS IN YOUNG MAMMALS

1928 ◽  
Vol 11 (4) ◽  
pp. 349-356 ◽  
Author(s):  
T. J. B. Stier ◽  
G. Pincus
Keyword(s):  
Temperature Control ◽  
Environmental Temperature ◽  
Internal Temperature ◽  
Critical Temperatures ◽  
Temperature Characteristics ◽  
Controlling System ◽  
Old Mice ◽  
Insight Into ◽  
Respiratory Movements

The internal temperature of 2 day old mice deviates by +0.01° to +3.0°C. from the environmental temperature over a range of 24°. The undeveloped temperature control allows rhythmic activities in this mammalian material to be readily subjected to the analysis afforded by temperature characteristics, and thus makes possible some insight into the physicochemical events controlling vital processes in entire uninjured mammals. The thermal increments and critical temperatures obtained point to a similarity in the controlling system of reactions for both homothermic and poikilothermic organisms. For frequency of respiratory movements the increments 12,340 (19.6° to 35.2°C.); 28,340 or 36,500 (15.5° to 19.6°C.) are most frequently found (thirteen cases). Rarely µ = 8,450, 33,000, or 18,340 (two cases). The last increment is either associated with µ = 36,000 below 20°, or extends unbroken throughout the whole range (one case).

scholarly journals Running enhances spatial pattern separation in mice

2010 ◽  
Vol 107 (5) ◽  
pp. 2367-2372 ◽  
Author(s):  
David J. Creer ◽  
Carola Romberg ◽  
Lisa M. Saksida ◽  
Henriette van Praag ◽  
Timothy J. Bussey
Keyword(s):  
Physical Activity ◽  
Spatial Pattern ◽  
Hippocampal Neurogenesis ◽  
Pattern Separation ◽  
Regular Exercise ◽  
Brain Health ◽  
Voluntary Running ◽  
Spatial Pattern Separation ◽  
Cell Genesis ◽  
Old Mice

Increasing evidence suggests that regular exercise improves brain health and promotes synaptic plasticity and hippocampal neurogenesis. Exercise improves learning, but specific mechanisms of information processing influenced by physical activity are unknown. Here, we report that voluntary running enhanced the ability of adult (3 months old) male C57BL/6 mice to discriminate between the locations of two adjacent identical stimuli. Improved spatial pattern separation in adult runners was tightly correlated with increased neurogenesis. In contrast, very aged (22 months old) mice had impaired spatial discrimination and low basal cell genesis that was refractory to running. These findings suggest that the addition of newly born neurons may bolster dentate gyrus-mediated encoding of fine spatial distinctions.

Potential use of IL-7 and IL-15 for ex vivo generation of LAK.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15201-e15201
Author(s):  
Svetlana Yu. Filippova ◽  
Oleg I. Kit ◽  
Anastasia O. Sitkovskaya ◽  
Elena Yu. Zlatnik ◽  
Inna A. Novikova ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Sorting ◽  
Scientific Literature ◽  
Nk Cell ◽  
Ex Vivo ◽  
Control Sample ◽  
Magnetic Cell Sorting ◽  
Potential Use ◽  
Number Of Cells ◽  
Control Samples

e15201 Background: A review of scientific literature has shown that IL-2 is most often used for the LAK generation, while the potential of other NK-stimulating interleukin cells remains poorly understood. In this study, we investigated the effect of IL-7 and IL-15 on ex vivo LAC generation. Methods: A fraction enriched in NK cells was isolated by magnetic cell sorting with the NK Cell Isolation Kit (#130-092-657, Miltenyi Biotec, Germany) from PBMC in 11 patients with stage II-III breast cancer without treatment. Cells were introduced into a 6-well 3x105 plate in RPMI medium (Gibco, USA) supplemented with 10% FBS (Gibco, USA). Cytokines 40 ng/ml were added to the wells in 6 variants: 1) IL-15; 2) IL-2; 3) IL-7; 4) IL-15+IL-7; 5) IL-15+IL-7+IL-2; 6) control without cytokines. Cells were cultured at 5.0% CO2 and 37°C. Cells were counted with a hemocytometer daily for 5 days and on days 8, 9 and 10 of cultivation. Results: The number of NK cells in control samples gradually decreased: by 2 times on day 5 and by 3 times on day 10. On day 5, the number of NK cells was 1.5 times higher than in the control when cultured with IL-2, and 1.4 times higher when cultured with IL-7+IL-15. After 9 days, a statistically significant increase in the number of cells, compared to the control sample, was observed with the addition of IL-2 (1.6 times); IL-15 and IL-7+IL-15 (1.5 times). On day 10, significant differences from the control were found in most samples: the number of cells was higher in samples cultured with IL-2 and IL-7+IL-15 (1.9 times) and with IL-15 and IL-2+IL-7+IL-15 (1.7 times). IL-7 alone led to a gradual decrease in the number of cells, and on days 8, 9 and 10 it was lower than in the control samples. Conclusions: In general, the introduction of cytokines into the samples enriched with NK cells contributed to the preservation of this subpopulation on days 5-10 of cultivation. However, the use of IL-7 and IL-15, both alone and in combination, did not lead to a significant increase in LAK compared to the use of IL-2.

A Single Bout of Prolonged Exercise Increases VLDL-TG Clearance

2006 ◽  
Vol 38 (Supplement) ◽  
pp. S484
Author(s):  
Yiannis E. Tsekouras ◽  
Dimitrios Bougatsas ◽  
Amalia E. Yanni ◽  
Stavros A. Kavouras ◽  
Labros S. Sidossis
Keyword(s):  
Prolonged Exercise ◽  
Single Bout
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