bluuebunny/crossref_metadata_2025_split huggingface dataset:
Not all skeletal muscle fibers depend on the myoprotection of KATP channels during fatigue (1102.15)
Authors: Renaud Jean‐Marc , Selvin David 
Published: June 2021

During fatigue, KATP channels are crucial in reducing action potential amplitude to eventually lower Ca2+ release by sarcoplasmic reticulum, which helps preserve ATP during a metabolic stress by decreasing Ca2+ ATPase and myosin ATPase activity. In the absence of KATP channel activity, skeletal muscle muscles suffer major contractile dysfunctions, which lead to faster fatigue rate because of fiber damage. In our studies at 37°C, we have observed a tremendous variability in the fatigue kinetics among mouse single FDB muscle fibers. Under control conditions, such variability is expected as fatigue resistance is in the order of type I>IIA>IIX>IIB (note IIB fibers are not present in FDB). However, we also observed a large variability in fatigue kinetics when KATP channels are completely blocked with 10 µM glibenclamide. Our results suggest that the importance of the KATP channel for myoprotection during fatigue is in the order of type IIX > IIA > I types, an order similar to the difference in KATP channel content between fiber types; i.e., the KATP channels are the most important in glycolytic fibers and the least important in oxidative fibers.Grant Funding Source: NSERC
Wnt3a potentiates myogenesis in C2C12 myoblasts through the modulation of intracellular calcium and activation of the β‐catenin signaling pathway (1102.23)
Authors: Huang Jian , Mo Chenglin , Bonewald Lynda , Brotto Marco 
Published: June 2021

Our research group has been investigating the biochemical crosstalk between bones and muscles. Wnts are secreted by bone cells and have a significant potential to directly influence muscle function. Our previous studies demonstrated potent myogenic effects of Wnt3a at a concentration of 10ng/ml. We now present new evidence that as low as 0.5ng/ml can significantly increase myogenic differentiation, which was confirmed morphologically and immunohistochemically. Wnt3a also promoted translocation of β‐catenin to the nucleus of myocytes/myotubes, suggesting that Wnt3a might lead to the downstream activation of muscle regulatory factors. Intriguingly, the potent effect of Wnt3a on stimulating the activation of the β‐catenin signaling pathway in C2C12 cells strongly correlated with the appearance of intracellular calcium oscillations in myotubes measured with Fura‐2. In agreement, focused qRT‐PCR arrays revealed a 6‐fold increase in IP3‐R1 and IP3R3, also revealed that Wnt3a promoted overexpression of myogenic markers (MyoD, MyoG, MHC), and downstream genes of the β‐catenin pathway (Fhl1 and Numb). We propose that Wnt3a acts through the modulation of intracellular calcium, resulting in translocation of β‐catenin that in turn enhances expression of muscle regulatory factors.Grant Funding Source: NIH‐NIA P01 AG039355 (LB, MB), Dale and Dorothy Thompson Endowment Fund (MB) and Missouri Life Scien
Physical inactivity promotes contractile dysfunction at the whole tissue, cellular and molecular levels in older adults (1102.29)
Authors: Callahan Damien , Miller Mark , Beynnon Bruce , Slauterbeck James , Toth Michael 
Published: June 2021

Age‐related deficits in skeletal muscle function are likely potentiated by corresponding reductions in volitional physical activity. Our objective was to investigate the effects of chronic muscle disuse by comparing structural and functional properties of skeletal muscle between healthy older adults with limited physical mobility secondary to knee osteoarthritis (Disuse; n=16) and healthy, recreationally‐active older adults (Controls; n=15). Knee extensor strength and cellular and molecular contractile characteristics were assessed from vastus lateralis muscle biopsies. Isometric and isokinetic knee extensor strength were reduced (34‐43%; p<0.01 for all) with disuse, as was single fiber force production in MHC I (18%; p 0.1 for all). Myosin‐actin cross‐bridge kinetic parameters were reduced in MHC I with disuse, as evidenced by prolonged actin‐myosin attachment time (+20%; p <0.01), but not in MHC IIA or IIA/X fibers. A strong trend towards more (+23%; p = 0.06) strongly‐bound cross‐bridges was observed in MHC I fibers with disuse. Considering similar MHC I tension between groups, these data suggest intrinsic impairments in molecular level force production/transmission with disuse. In summary, although cellular level deficits in force production are explained by atrophy, molecular level changes, which are independent of fiber size, may contribute to impaired whole muscle performance observed with chronic muscle disuse.Grant Funding Source: Supported by NIH AG033547
Exon 12 of slow skeletal troponin t affects calcium sensitivity of force development and interactions with other thin filament components (1102.30)
Authors: Pinto Jose Renato , Xu Qian , Parvatiyar Michelle , Oh Won Chan , Potter James , Gomes Aldrin 
Published: June 2021

Little information exists concerning the functional roles of the human slow skeletal troponin T isoforms (HSSTnT isoforms) in slow skeletal muscle. Three HSSTnT isoforms have been found in human slow skeletal muscle: HSSTnT1 (+ exons 5 and 12), HSSTnT2 (+5, ‐12), and HSSTnT3 (‐5, ‐12). Another potential isoform HSSTnT‐Hyp (‐5, +12) was recently found at the mRNA level. The objective of this study was to determine the physiological role of these SSTnT isoforms in slow skeletal muscle. To investigate these SSTnT isoforms several methods including skinned fiber mechanics, peptide spot blot, and mammalian two‐hybrid assays were utilized. Skinned rabbit slow soleus muscle fibers were displaced with HSSTnT1, 2, 3 or Hyp and reconstituted with the human slow skeletal troponin I (HSSTnI)/human cardiac troponin C (HCTnC) complex. The calcium sensitivity increased between SSTnT isoforms: isoform 1 (pCa50 = 5.74) < Hyp isoform (pCa50 = 5.80) < isoform 2 (pCa50 = 5.81) < isoform 3 (pCa50 = 5.84). In a reconstituted skeletal muscle system, the HSSTnT 1‐3 isoforms had similar actomyosin ATPase activation or inhibition in the presence or absence of calcium. Peptide spot blot analysis revealed novel interactions between HSSTnT peptides and HCTnC, RSTm and HCTnI. Mammalian two‐hybrid studies showed that the alternatively spliced regions affect the interaction of HSSTnT with other thin filament components. These results suggest that the functional differences that occur between HSSTnT isoforms may be partially due to alternative splicing of exon 12. Overall, HSSTnT isoforms were found to have distinct functional properties in slow skeletal muscle regulation and are likely to be relevant for the understanding of skeletal muscle diseases.Grant Funding Source: UC Davis research funds and NIH
Effects of total knee arthroplasty on markers of muscle damage two hours after surgery (1102.33)
Authors: Hocker Austin , Jewett Brian , Shah Steven , Lantz Brick , Dreyer Hans 
Published: June 2021

Total knee arthroplasty (TKA) results in rapid muscle atrophy, decreased strength, and functional mobility limitations. Our prior reports on the acute effects of ischemia and reperfusion during TKA suggests decreased protein synthesis, increased protein degradation, and activation of the endoplasmic reticulum (ER) stress response in skeletal muscle. The purpose of this experiment was to determine if protein and transcript markers of protein synthesis, degradation, and ER stress remained elevated two hours after TKA. We studied 60‐80 year old patients before and two hours after primary TKA. Muscle biopsies were obtained in the operating room immediately before tourniquet application, at maximal ischemia, and two hours after reperfusion. Our preliminary data show the fraction of spliced XBP1 transcript increased 124% during ischemia (p = .11) and 104% after reperfusion (p < .05) relative to baseline. Protein levels of phosphorylated 4EBP1 (Thr37/46) decreased 34% during ischemia (p < .05) and 20% after reperfusion (not significant) relative to baseline. Phosphorylation of AKT (Ser473) decreased 69% during ischemia (p = .10) and nearly returned to baseline after reperfusion. Interestingly, transcript levels of ATF4 and BIP were decreased during both ischemia and recovery (p < .05) and ERDJ4 and CHOP expression was not significantly different relative to baseline during ischemia or after reperfusion. Two hours after TKA muscle cell cross sectional area was increased 34% relative to baseline. These preliminary results suggest that ischemia and reperfusion during TKA induce changes in muscle metabolism that persist two hours after surgery.Grant Funding Source: Supported by K01HD057332
Bone marrow inoculation of Walker 256 tumor cells in rats as a model of cancer cachexia (1102.36)
Authors: Alves Christiano , de Almeida Ney , das Neves Willian , Gutierrez Vanessa , Voltarelli Vanessa , Cury Yara , Gualano Bruno , Seelaender Marília , Lancha Junior Antonio , Brum Patricia 
Published: June 2021

Bone marrow inoculation of Walker 256 tumor cells in rats as a model of cancer cachexia Christiano R. R. Alves, Ney R. de Almeida, Willian das Neves, Vanessa P. Gutierrez, Vanessa Voltarelli, Yara Cury, Bruno Gualano, Marília Seelaender, Antonio H. Lancha Junior, Patricia C. Brum. University of São Paulo, São Paulo, Brazil.The aim of this study was to standardize a model of cancer cachexia in rats by inoculating Walker 256 tumor cells in bone marrow. Male Wistar rats were inoculated with Walker 256 tumor cells in the bone marrow by an osteotomy in femur (Walker group). Control rats were submitted to sham osteotomy (Control group). Walker was compared to the Control group by unpaired Student's t‐test. The significance level was previously set at p < 0.05. After the osteotomy, Walker group showed 16 days of survival on the average with 100% mortality rate after 23 days paralleled by lower body mass (‐8.8%; p = 0.03) and food intake (‐30.1%; p < 0.001) than Control group. In addition, Walker group decreased in vivo skeletal muscle function, assessed by both treadmill maximal incremental test (‐52.7%) and deambulation test (‐21.1%) (p < 0.001). Walker group displayed plantaris, gastrocnemius and triceps atrophy (p < 0.05 for all), which was not observed in soleus (p > 0.05). Additionally, lower citrate synthase activity and oxidized/reduced glutathione ratio were observed in plantaris (p < 0.05) but not in soleus (p > 0.05) of Walker group. These data provide evidence for oxidative metabolism dysfunction and redox imbalance in muscles with predominance of glycolytic fibers (i.e. plantaris), but not in muscles with predominance of oxidative fibers (i.e. soleus). Collectively, our results suggest that bone marrow inoculation of Walker 256 tumor cells in rats is a new model of severe cancer‐induced muscle atrophy selective to glycolytic fibers.Grant Funding Source: FAPESP (process: 2012/02528‐0)
AT1 receptor blocker attenuates mechanical ventilation‐induced atrophy and oxidative stress in the diaphragm muscle (1102.39)
Authors: Kwon Oh‐Sung , Smuder Ashley , Sollanek Kurt , Wiggs Michael , Talbert Erin , Scott Powers 
Published: June 2021

Background: Mechanical ventilation (MV) is a method of maintaining adequate gas exchange in patients who are unable to sustain adequate alveolar ventilation on their own. Recently, our lab demonstrated that Angiotensin II (Ang II) is a possible mechanism that causes MV‐induced diaphragm muscle atrophy. During MV, elevation of Ang II induces Reactive Oxygen Species (ROS) emission from mitochondria and results in activation of key proteases, calpain and caspase‐3, in the diaphragm. To determine Ang II is a required upstream signal for MV‐induced diaphragm muscle atrophy and contractile dysfunction, we used AT1 receptor blocker (Losartan) and ACE inhibitor (Enalapril), which prevent the elevation of plasma Ang II levels during MV.Methods: Adult female rats were randomly assigned to one of six experimental groups (n =12 each) (1) Spontaneous breathing (SB) with salin, (2) SB with Losartan (LOS), (3) SB with Enalapril (ENA), (4) MV with salin, (5) MV with LOS, (6) MV with ENA. Dependent measures included plasma Ang II levels, diaphragmatic muscle fiber cross‐sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm.Results: ENA attenuates increased circulating Ang II levels during 12 hours prolonged MV but LOS does not. However, only LOS attenuated MV‐induced diaphragm muscle atrophy. As well as, LOS attenuated MV‐induced mitochondrial dysfunction, ROS production, and proteasome activity during.Therefore, Ang II does not appear to be a possible upstream mechanism to prevent MV‐induced diaphragm muscle atrophy. AT1 receptor blocker, losartan has an antioxidant effect and attenuates MV‐induced VIDD. Therefore, the results of our experiments could lead to human clinical trials using losartan as a therapeutic intervention to prevent VIDD.
Role of small heat shock proteins in muscle under chronic hyperglycemia (1102.42)
Authors: Reddy Vadde , Reddy Geereddy 
Published: June 2021

Role of small heat shock proteins in muscle under chronic hyperglycemia V. Sudhakar Reddy1, G. Bhanuprakash Reddy1 1Department of Biochemistry, National Institute of Nutrition, Hyderabad, India Objective: To study the expression of small heat shock proteins (sHsp) and their localization in diabetic rat muscle.Methods: Diabetes was induced in rats and maintained on hyperglycemia for a period of 12 weeks. The expression of sHsp and phosphorylated sHsp was analysed by qRT‐PCR, immunoblotting. The translocation of phosphorylated sHsp (pS82‐Hsp27, pS59‐αB‐crystallin; αBC) was analyzed by detergent solubility assay and co‐immunoprecipitation. The cell death was analysed by assessing the levels bcl‐2, bax and cleaved caspase‐3. The interaction of αBC with bax was analyzed by co‐immunoprecipitation Results: Out of 10 sHsp, 7 sHsp were detected in muscle. Among them, increased expression of αBC was seen diabetic muscle. Furthermore, detergent soluble assay and co‐immunoprecipitation studies confirmed the translocation and interaction of phosphorylated sHsp with cytoskeleton (desmin) under diabetic conditions. Diabetes induced the cell death as assessed by the levels of cleaved caspase‐3, bax and bcl‐2. Moreover, diabetes reduced the interaction of αBC with bax.Conclusion: There was increased expression of αBC under hyperglycemic conditions. Further, chronic hyperglycemia induced the translocation of pS82‐Hsp27 and pS59‐αBC from cytoplasm to a striated sarcomere at or near z‐lines and intercalated discs. Altered interaction of αBC with bax seems to influence cell death in diabetic muscle.
Myostatin expression and high fat diet effects on skeletal muscle and adipose metabolism in mouse (1102.45)
Authors: Constantinescu Silvana , Abraham Andrea , Reisz‐Porszasz Suzanne 
Published: June 2021

We explored the effects of myostatin (Mst) expression and high fat diet (HFD) on skeletal muscle (SM) and adipose tissues (AT) metabolic profiles in transgenic mice overexpressing Mst (TG). To investigate the effects of Mst on SM and AT in wild‐type (WT) and TG mice, and the correlation between Mst and insulin resistance, we measured mRNA levels and protein expression of Mst, several intermediates from the insulin signaling pathway and analyzed the metabolic profile of both tissues using METABOLON. Methods: Adult male mice (6 mice/group) were kept on control diet (CD) and HFD for 4 weeks; glucose tolerance was measured before and after the diet; blood, SM and AT were collected. Results: Metabolon heat‐map analysis showed that Mst in TG mice on CD or HFD increased (95%; P<0.05) several glycolytic intermediates in SM suggesting that glycolysis and glucose uptake is elevated by Mst overexpression. TG mice on CD had lower (P>0.05) levels of free fatty acids (FFAs) compared to WT in SM and AT. HFD increased (25%) the levels of FFAs in SM compared to AT in WT and TG. Conclusion: WT‐SM responded to HFD with a rise (62%) in fatty acid oxidation (FAO); TG‐SM with HFD showed no change (P>0.05) in FAO. TG‐AT responded to HFD with a rise in triacylglycerol synthesis (12%) and a decrease in FAO. These data suggest that genetic modification of Mst expression affected primarily SM glucose utilization parallel with decreased FAO in AT in adult mice.Grant Funding Source: NIH/NIGMS: SC1GM089648
Muscle fibrosis due to loss of desmin increases muscle stiffness due to an increased number of perimysial collagen cables (1102.8)
Authors: Gillies Allison , Lieber Richard 
Published: June 2021

Skeletal muscle stiffness increases with injury and disease, yet the structural basis of stiffness is unknown. The purpose of this study was to quantify perimysial collagen in a model of skeletal muscle fibrosis (desmin knockout, des‐/‐) to determine if increased stiffness correlates with increased volume fraction of these structures. Stereology was performed on mouse 5th toe extensor digitorum longus (EDL) muscles to quantify perimysial collagen volume fraction and mechanical testing was performed to determine muscle stress at incremental sarcomere lengths. Stereology indicated a significantly higher volume fraction of collagen fibrils in cables in des‐/‐ compared to wt (Table 1). Tangent stiffness of des‐/‐ compared to wt (Fig. 1) was four times greater (p<0.05). In des‐/‐ muscle, perimysial collagen cable volume increased concurrent with stiffness while no increase was observed in endomysial collagen, implicating the perimysial collagen structures in increased stiffness at the whole muscle level, not just increased collagen in general. These results suggest that therapies targeting perimysial collagen cables may improve function in fibrotic skeletal muscle.
Table 1. Volume fraction of muscle components as percent EDL volume. Mean ± SEM, *p<0.05.

Muscle Component
Wild type (n = 8)
Desmin knockout (n = 8)

Myofibrils
59.2 ± 2.4
59.2 ± 2.8

Mitochondria
9.53 ± 0.8
8.20 ± 1.0

Myonuclei
0.55 ± 0.07
0.78 ± 0.13

Satellite cells
0.02 ± 0.009
0.009 ± 0.009

Fibroblasts
0.59 ± 0.14
0.74 ± 0.11

Single collagen fibrils
1.51 ± 0.31
1.26 ± 0.13

Collagen fibrils in cable
2.45 ± 0.26
4.15 ± 0.55*

Basement membrane
2.18 ± 0.23
1.83 ± 0.08
Leucine supplementation partially preserves neuromuscular activation during bed rest (1103.5)
Authors: Mettler Joni , Doucet Barbara , English Kirk , Bennett Sydney , Paddon‐Jones Douglas 
Published: June 2021

We examined the effect of leucine supplementation on neuromuscular activation of sub‐maximal and maximal voluntary muscle contraction (MVC) in middle‐aged adults during 14 days of bed rest (BR). Participants (n = 10, 50.4 ± 1.0 y) in this randomized, double‐blind control 14 day BR study were assigned to a leucine (LEU, 0.06 g∙kg∙meal‐1 leucine) or control (CON) group. Surface electromyography (EMG) and torque were recorded from the vastus lateralis muscle during isometric knee extension at 20% (10s) and at 50%, 80% and 100% MVC (5s each) pre‐post BR and analyzed for root mean square (RMS) and median frequency (MF) EMG. Following BR, MVC (p < 0.001) decreased in both groups with no difference between groups. RMS EMG during 100% MVC decreased in CON post‐BR (p < 0.05), but was maintained in LEU and no difference in MF EMG pre‐post BR for either group (p > 0.05). Despite the decrease in MVC in both groups, CON RMS EMG was higher post‐BR during all sub‐maximal contractions while LEU RMS EMG did not change at 20% and was lower at 50% and 80% MVC post‐BR. Leucine may facilitate neuronal protective mechanisms that preserve motor neuron excitability and attenuate strength loss during prolonged physical inactivity.Grant Funding Source: Supported by NSBRI NNJ08ZSA002N, NIA P30 AG024832, NIH 1UL1RR029876‐01
Effects of physical training on thermoregulation during exercise in spontaneously hypertensive rats (1104.1)
Authors: Santiago Henrique , Leite Laura , Lima Paulo Marcelo , Prímola‐Gomes Thales , Rodrigues Ana Cristina , Coimbra Cândido 
Published: June 2021

The influence of physical training on heat balance and exercise performance in spontaneously hypertensive rats (SHR) was assessed. After physical training (8 wks), trained (T) and untrained (UT) SHR (n=6) and control Wistar rats (n=8) were submitted to incremental running until fatigue while body (Tb) and tail (Ttail) temperatures were recorded. T animals had increased workload (10.2 ± 0.7 kgm SHR‐T vs 5.9 ± 0.3 kgm SHR‐UN, 22.9 ± 1.4 kgm Wistar‐T vs. 10.9 ± 0.8 kgm Wistar‐UN; p < 0.05), however, SHR‐T and SHR‐UN demonstrated a reduction of 42% and 31%, respectively, in time of exercise in comparison with corresponding controls (p < 0.05). Tb increase was similar during exercise within the same lineage but SHR exhibited higher Tb variation from 14 min of exercise until fatigue (2.4 ± 0.2 °C SHR‐T vs. 1.4 ± 0.1 °C Wistar‐T; 1.8 ± 0.1 °C SHR‐UN vs. 1.1 ± 0.2 °C Wistar‐UN; p < 0.05). Moreover, although all groups had similar Ttail variation during exercise, SHR had lower Ttail at fatigue (30.1 ± 0.4 °C SHR‐T vs. 31.4 ± 0.3 °C Wistar‐T; 29.1 ± 0.5 °C SHR‐UN vs. 31.0 ± 0.3°C Wistar‐UN; p < 0.05), indicating an inferior vasodilation potential. The data show that hypertension aggravates the exercise‐induced hyperthermia due to lower heat dissipation through tail vasodilation, which contributes to the reduction in exercise performance.Grant Funding Source: CNPq, FAPEMIG and CAPES
Determinants of core temperature thresholds for exercise ventilation (1104.23)
Authors: White Matthew , Yogev Assaf , Beaudin Andrew , Martin Des , Walsh Michael 
Published: June 2021

Correlation and multiple regression analysis were employed to assess for human physical and physiological predictors of esophageal temperature (TES) thresholds for pulmonary ventilation during exercise (VE). It was hypothesized these TES thresholds would be positively associated to peak oxygen consumption (VO2PEAK) and thermolytic responses as well as negatively associated to the chemosensitivity of breathing. The SFU Office of Research Ethics approved the study. Twenty‐three volunteers participated 2 studies. They were 27.8±7.9 years of age (mean ± SD), 71.9±7.2 kg in weight and 1.76±0.06 m in height. They had a Body Surface Area (BSA) of 1.87±0.1 m2 and a Body Mass Index (BMI) of 23.4±2.4 kg/m2. Twenty‐three volunteers performed incremental cycle ergometer exercise from rest to the point of exhaustion. A second group of 9 volunteers performed a hyperoxic‐hypercapnic, modified Read rebreathing test during normothermia and hyperthermia. For correlation and multiple regression analyses the dependent outcome variables were TES thresholds for ventilatory equivalents for oxygen (VE/VO2) and carbon dioxide (VE/VCO2). For the same analyses the independent variables included age, weight, height, BSA, BMI, VO2PEAK, the ventilatory recruitment threshold and slope from Read rebreathing plots and TES thresholds for onsets of eccrine sweating (ESW) and cutaneous blood velocity (CBV). Results indicated significant positive correlations between TES thresholds for VE/VO2 and VE/VCO2 with VO2PEAK (both r=0.42, p<0.05) and each of the TES thresholds for the onset of ESW and CBV (0.72<r<0.78, p<0.01). Multiple regression analysis gave the TES threshold for ESW as the single significant predictor of TES thresholds for VE/VO2 and VE/VCO2 (both R=0.72, p<0.05). In conclusion, TES thresholds for exercise ventilation were positively associated to VO2PEAK and prediction of these ventilation thresholds were made with TES thresholds for eccrine sweating.Grant Funding Source: Supported by NSERC and CFI