scholarly journals OR-035 Effect of Aerobic Training on the Exercise Capacity of Apelin Knock-out Mice

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Lu Yan ◽  
Tieying Li ◽  
Ying Zhang
Keyword(s):  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Oxygen Uptake ◽  
Exercise Capacity ◽  
Aerobic Training ◽  
Movement Time ◽  
Wild Type ◽  
Running Speed ◽  
Knock Out ◽  
Knock Out Mice

Objective Aerobic training is considered to be an effective way to enhance the body’s exercise capacity which is closely related to the improvement of skeletal muscle energy metabolism. And as a new myokine, apelin has been found to play a key role in regulating the energy metabolism of skeletal muscle. However, whether the loss of apelin gene affects exercise capacity and what role aerobic training play in it remains unknown. This study was designed to investigate the effect of apelin on exercise capacity during aerobic training and to provide a theoretical basis for the mechanism of aerobic exercise affecting exercise capacity. Methods Male C57BL/6J wild type mouse(n=20) and apelin knock-out mouse(n=20) were assigned by random allocation to four groups(n=10): wild type control(WC), wild type exercised(WE), apelin knock-out control(KC) and apelin knock-out exercised(KE). Exercise training consisted of treadmill running 60 minutes/day ×6 days/week for 4 weeks. The training intensity corresponded to the 70-75% maximum oxygen uptake of mice. The running speed was 15m/min with an incline of +5° in the first 2 weeks and subsequently adjusted to 20m/min according to the maximum oxygen uptake in the last 2 weeks. On the day after training, all groups were forced to perform a incremental exercise test to exhaustion. This test was started with an incline of +5°and a speed of 10 m/min for 5 min. After this initial phase, the speed was progressively increased by 3m/min every 3 min until animal exhausted. The maximum running speed, movement time and distance were recorded during the test. Results Compared with group WC, the maximum running speed, movement time and distance of group KC were significantly decreased(P<0.01). And the maximum running speed, movement time and distance of group KE were clearly higher than those of group KC(P<0.01). There is no significant difference between group WE and group WC, and between group KE and group WE. Conclusions The exercise capacity of mice was significantly decreased because of knocking out the apelin gene, and the exercise ability of apelin knock-out mice can be clearly enhanced by aerobic training.

Functional characterization of the H+/K+ ATPase in wild type and gastrin knock-out mice

2007 ◽  
Vol 45 (05) ◽  
Author(s):  
A Schnur ◽  
P Hegyi ◽  
V Venglovecz ◽  
Z Rakonczay ◽  
I Ignáth ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Wild Type ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Postnatal changes of interleukin-18 receptor immunoreactivity in neurons of the retrosplenial cortex in wild-type and interleukin-18 knock out mice

2017 ◽  
Vol 94 (3) ◽  
pp. 93-99
Author(s):  
Tetsu HAYAKAWA ◽  
Masaki HATA ◽  
Sachi KUWAHARA-OTANI ◽  
Hideshi YAGI ◽  
Haruki OKAMURA
Keyword(s):  
Retrosplenial Cortex ◽  
Wild Type ◽  
Interleukin 18 ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 737 ◽  
Author(s):  
Zsolt Sarang ◽  
Tibor Sághy ◽  
Zsófia Budai ◽  
László Ujlaky-Nagy ◽  
Judit Bedekovics ◽  
...  
Keyword(s):  
Transglutaminase 2 ◽  
Tissue Homeostasis ◽  
Apoptotic Cells ◽  
Wild Type ◽  
Integrin Receptors ◽  
Macrophage Differentiation ◽  
Phagocytic Capacity ◽  
Knock Out ◽  
Knock Out Mice ◽  
Number Of Cells

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvβ3/β5 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage.

scholarly journals Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2

2019 ◽  
Vol 127 (5) ◽  
pp. 1267-1277
Author(s):  
Linjia Wang ◽  
Simin Yang ◽  
Lu Yan ◽  
Hao Wei ◽  
Jianxiong Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Treadmill Exercise ◽  
Related Factor ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypoxia Preconditioning ◽  
Nrf2 Knockout ◽  
Exercise Induced ◽  
Induced Changes

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle. NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.

NAD(P)H Oxidase-derived Oxidative Stress Impairs Energy Metabolism in Skeletal Muscle and Limit Exercise Capacity

2007 ◽  
Vol 13 (6) ◽  
pp. S43-S44
Author(s):  
Naoki Inoue ◽  
Shintaro Kinugawa ◽  
Yukihiro Ohta ◽  
Shouji Matsushima ◽  
Hiroyuki Tsutsui
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Exercise Capacity

One-Mutation Model Can Explain Age Incidence in AML Carrying Nucleophosmin (NPM1) Mutations.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4312-4312
Author(s):  
Arcangelo Liso ◽  
Filippo Castiglione ◽  
Antonio Cappuccio ◽  
Fabrizio Stracci ◽  
Christian Thiede ◽  
...  
Keyword(s):  
Leukemic Cells ◽  
Specific Rate ◽  
Wild Type ◽  
Genetic Event ◽  
Knock Out ◽  
Incidence Data ◽  
Molecular Alterations ◽  
Moran Process ◽  
Mutation Model ◽  
Knock Out Mice

Abstract Acute myeloid leukemia (AML) carrying nucleophosmin (NPM1) mutations and cytoplasmic NPM (NPMc+ AML) accounts for about one-third of all AML patients, and exhibits distinctive biological and clinical features. The role of NPM1 mutations in leukemogenesis remains elusive. Mathematical models have been developed that, starting from cancer incidence data, allow to infer the somatic mutation rate, or the number of genetic events required to cause cancer. We collected data on age at diagnosis of AML patients from four centers in three different countries, and calculated age-specific rates of NPMc+ AML. A total of 4,155 AML patients were investigated. NPM1 mutations these were detected in 1288. Patients carrying NPM1 mutations with age below 20 years and above 59 years were excluded from the study because of the low number of younger cases and because older patients are not always referred to major institutions for diagnosis and treatment. To investigate NPMc+ AML we adapted one-mutation model published by Michor et al (PNAS, 2006; 103: 14931). The mathematical model consider a population of N (hemopoietic stem) cells that at beginning are wild-type. These cells proliferate according to the Moran process. The growth follows a logistic law with a saturation term. Our process follows the “classical” Moran process up to the appearance of a successful mutant. After that, the clone expands to a limiting population size. This is done to account for the dramatic expansion of the initial compartment peculiar of AML. Finally the rate of AML detection is proportional to the number of mutated cells. Experimental incidence curves of AML in Germany (Ge), Netherlands (Nl), and Italy (It) plotted simultaneously with predicted one-mutation model estimates are shown in Fig. 1. Linear regression of curves representing age-specific rate of diagnoses per year showed similar slopes (about 4 on a double-log scale) in different countries. The one-event model reproduces well the “exponential phenotype” of NPMc+ AML. In conclusion the model is in accordance with the hypothesis that NPM1 mutations by themselves are sufficient to cause NPMc+ AML. Alternatively, it is still possible that NPM1 mutations might cooperate with other molecular alterations to cause AML. In particular, since NPM1 mutations cause haploinsufficiency of wild-type NPM in leukemic cells and in knock-out mice NPM haploinsufficiency results in a MDS-like syndrome and given that the NPM1 mutant has oncogenic properties, these alterations could act in concert to cause AML. Indeed, the effect of these two alterations occurring simultaneously could be seen as a single genetic event. Figure Figure

Contribution of Lipocalin-2 from Both Myeloid Cells and Epithelium/Liver Is Required for Optimal Resistance to K. Pneumonia Infection

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 883-883
Author(s):  
Elisabeth Præstekjær Cramer ◽  
Sara Louise Dahl ◽  
Björn Rozell ◽  
Kasper Jermiin Knudsen ◽  
Kim Thomsen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Epithelial Cells ◽  
Conflicts Of Interest ◽  
Neutrophil Migration ◽  
Myeloid Cells ◽  
Infection Model ◽  
Lipocalin 2 ◽  
Wild Type ◽  
Knock Out ◽  
Knock Out Mice

Abstract Introduction NGAL/lipocalin-2 is a siderophore-binding protein stored in high amounts in specific granules of neutrophils. In addition, expression and constitutive secretion of lipocalin-2 can be induced in macrophages and epithelial cells under inflammatory conditions. In mice, lipocalin-2 is furthermore an acute phase-protein. Siderophores are the strongest iron chelators known and are produced by certain microorganisms to retrieve soluble iron from the host. By preventing uptake of siderophore bound iron, lipocalin-2 is bacteriostatic to bacteria that are dependent on this mechanism for uptake of iron. In accordance, lipocalin-2 knock-out mice are susceptible to infection by such bacteria. It is, however, not known whether it is the induced production of lipocalin-2 in epithelial cells and liver or the delivery of lipocalin-2 from infiltrating myeloid cells (neutrophils and macrophages) that is most important for these mechanisms of host defense against invading pathogens. Methods To study the contributions of lipocalin-2 from epithelial cells and liver compared to infiltrating myeloid cells, we used a Klebsiella pneumoniae lung infection model in C57BL/6 mice with chimeric expression of lipocalin-2. Bone marrow transplantation of lethally irradiated mice generated wild type-mice with a lipocalin-2 knock-out bone marrow (WT/KO) expressing lipocalin-2 in epithelium and liver but not in myeloid cells, and conversely knock out-mice with wild-type bone marrow (KO/WT) expressing lipocalin-2 in myeloid cells and not in epithelium and liver. Wild-type mice transplanted with wild-type bone marrow (WT/WT) and knock-out mice transplanted with knock-out bone marrow (KO/KO) were also generated. After 7 weeks of reconstitution, mice were nasally challenged with K. pneumoniae for induction of pneumonia and potential dissemination of the infection. The mice were sacrificed twenty-four hours after inoculation and examined. Results Lipocalin-2 levels in broncho alveolar lavage (BAL) fluid were comparable between WT/KO and KO/WT mice. Consistent with this, no difference in bacterial counts (CFU) in BAL fluid was seen. No differences in spleen CFUs were evident between the two chimeric subgroups WT/KO and KO/WT despite a quantitatively larger mean lipocalin-2 plasma level in WT/KO mice (almost 50 times) derived from epithelium and liver compared to the contribution from myeloid cells in KO/WT mice. However, mean CFU in spleen homogenates from KO/KO mice were more than 870 times higher compared to WT/WT mice. Both the lipocalin-2 contribution from myeloid cells and from epithelium and liver appeared to be indispensable judged by the higher spleen CFUs in mice lacking lipocalin-2 from either of the two compartments. Lipocalin-2 mRNA in the liver was present in equal amounts in mice with wild-type background despite the presence or absence of lipocalin-2 in the myeloid cells. No differences in neutrophil influx to the lungs were seen between groups as determined by MPO ELISA on lung homogenates. We conclude that lipocalin-2 derived both from myeloid cells and from epithelium and liver is required for full resistance to a siderophore-producing pathogen. Despite the higher levels of plasma lipocalin-2 in WT/KO mice compared to KO/WT mice, their bacteriostatic capacity is equal. The induction of lipocalin-2 in the liver is not dependent on the presence of lipocalin-2 in the myeloid cells, just as the migration of neutrophils to the infected lung is not, thus refuting a recent report that lipocalin-2 affects neutrophil migration. Disclosures No relevant conflicts of interest to declare.

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