Calpain-3 is autolyzed and hence activated in human skeletal muscle 24 h following a single bout of eccentric exercise

2007 ◽  
Vol 103 (3) ◽  
pp. 926-931 ◽  
Author(s):  
Robyn M. Murphy ◽  
Craig A. Goodman ◽  
Michael J. McKenna ◽  
Jason Bennie ◽  
Murray Leikis ◽  
...  
Keyword(s):  
Eccentric Exercise ◽  
Human Subjects ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Healthy Human ◽  
Calpain 3 ◽  
Torque Measurements

The function and normal regulation of calpain-3, a muscle-specific Ca2+-dependent protease, is uncertain, although its absence leads to limb-girdle muscular dystrophy type 2A. This study examined the effect of eccentric exercise on calpain-3 autolytic activation, because such exercise is known to damage sarcomeric structures and to trigger adaptive changes that help prevent such damage on subsequent exercise. Six healthy human subjects performed a 30-min bout of one-legged, eccentric, knee extensor exercise. Torque measurements, vastus lateralis muscle biopsies, and venous blood samples were taken before and up to 7 days following the exercise. Peak isometric muscle torque was depressed immediately and at 3 h postexercise and recovered by 24 h, and serum creatine kinase concentration peaked at 24 h postexercise. The amount of autolyzed calpain-3 was unchanged immediately and 3 h after exercise, but increased markedly (from ∼16% to ∼35% of total) 24 h after the exercise, and returned to preexercise levels within 7 days. In contrast, the eccentric exercise produced little autolytic activation of the ubiquitous Ca2+-activated protease, μ-calpain. Eccentric exercise is the first physiological circumstance shown to result in calpain-3 activation in vivo.

Impact of training status on LPS-induced acute inflammation in humans

2015 ◽  
Vol 118 (7) ◽  
pp. 818-829 ◽  
Author(s):  
J. Olesen ◽  
R. S. Biensø ◽  
S. Meinertz ◽  
L. van Hauen ◽  
S. M. Rasmussen ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Human Subjects ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Arterial Blood Flow ◽  
Vastus Lateralis Muscle ◽  
Training Status ◽  
Arterial Blood ◽  
Mrna Content ◽  
The Impact

The aim of the present study was to examine the impact of training status on the ability to induce a lipopolysaccharide (LPS)-induced inflammatory response systemically as well as in skeletal muscle (SkM) and adipose tissue (AT) in human subjects. Seventeen young (23.8 ± 2.5 yr of age) healthy male subjects were included in the study with eight subjects assigned to a trained (T) group and nine subjects assigned to an untrained (UT) group. On the experimental day, catheters were inserted in the femoral artery and vein of one leg for blood sampling and a bolus of 0.3 ng LPS/kg body wt was injected into an antecubital vein in the forearm. Femoral arterial blood flow was measured by ultrasound Doppler, and arterial and venous blood samples were drawn before (Pre) LPS injection and 30, 60, 90, and 120 min after the LPS injection. Vastus lateralis muscle and abdominal subcutaneous AT biopsies were obtained Pre and 60 and 120 min after the LPS injection. LPS increased the systemic plasma TNFα and IL-6 level as well as the TNFα and IL-6 mRNA content in SkM and AT of both UT and T. However, whereas the LPS-induced inflammatory response in SkM was enhanced in T subjects relative to UT, the inflammatory response systemically and in AT was somewhat delayed in T subjects relative to UT. The present findings highlight that training status affects the ability to induce a LPS-induced acute inflammatory response in a tissue-specific manner.

Exercise-induced translocation of Na+-K+ pump subunits to the plasma membrane in human skeletal muscle

2000 ◽  
Vol 278 (4) ◽  
pp. R1107-R1110 ◽  
Author(s):  
Carsten Juel ◽  
Jens Jung Nielsen ◽  
Jens Bangsbo
Keyword(s):  
Human Subjects ◽  
Vastus Lateralis ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Biopsy Material ◽  
Exercise Time ◽  
Fatigue Exercise ◽  
Vesicular Membrane ◽  
Exercise Induced ◽  
Short Time

Six human subjects performed one-legged knee extensor exercise (90 ± 4 W) until fatigue (exercise time 4.6 ± 0.8 min). Needle biopsies were obtained from vastus lateralis muscle before and immediately after exercise. Production of giant sarcolemmal vesicles from the biopsy material was used as a membrane purification procedure, and Na+-K+ pump α- and β-subunits were quantified by Western blotting. Exercise significantly increased ( P < 0.05) the vesicular membrane content of the α2-, total α-, and β1-subunits by 70 ± 29, 35 ± 10, and 26 ± 5%, respectively. The membrane content of α1 was not changed by exercise, and the densities of subunits in muscle homogenates were unchanged. The ratio of vesicular to crude muscle homogenate content of the α2-, total α-, and β1-subunits was elevated during exercise by 67 ± 33 ( P < 0.05), 23 ± 6 ( P < 0.05), and 40 ± 14% ( P = 0.06), respectively. It is concluded that translocation of subunits is an important mechanism involved in the short time upregulation of the Na+-K+ pumps in association with human muscle activity.

scholarly journals Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise

2009 ◽  
Vol 107 (5) ◽  
pp. 1600-1611 ◽  
Author(s):  
U. R. Mikkelsen ◽  
H. Langberg ◽  
I. C. Helmark ◽  
D. Skovgaard ◽  
L. L. Andersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Eccentric Exercise ◽  
Satellite Cells ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Cell Activity ◽  
Inflammatory Cells ◽  
Vastus Lateralis Muscle

Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working as a control (unblocked leg). Muscle biopsies were collected before and 8 days after exercise. Changes in satellite cells and inflammatory cell numbers were investigated by immunohistochemistry. Satellite cells were identified using antibodies against neural cell adhesion molecule and Pax7. The number of Pax7+cells per myofiber was increased by 96% on day 8 after exercise in the unblocked leg (0.14 ± 0.04, mean ± SE) compared with the prevalue (0.07 ± 0.02, P < 0.05), whereas the number of Pax7+cells was unchanged in the leg muscles exposed to the NSAID (0.07 ± 0.01). The number of inflammatory cells (CD68+or CD16+cells) was not significantly increased in either of the legs 8 days after exercise and was unaffected by the NSAID. The main finding in the present study was that the NSAID infusion for 7.5 h during the exercise day suppressed the exercise-induced increase in the number of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.

scholarly journals Determination of receptor occupancy in the presence of mass dose: [11C]GSK189254 PET imaging of histamine H3 receptor occupancy by PF-03654746

2016 ◽  
Vol 37 (3) ◽  
pp. 1095-1107 ◽  
Author(s):  
Jean-Dominique Gallezot ◽  
Beata Planeta ◽  
Nabeel Nabulsi ◽  
Donna Palumbo ◽  
Xiaoxi Li ◽  
...  
Keyword(s):  
Binding Sites ◽  
Human Subjects ◽  
Receptor Occupancy ◽  
Healthy Human ◽  
Positron Emission ◽  
Relationship Of ◽  
The Relationship ◽  
Pet Scans

Measurements of drug occupancies using positron emission tomography (PET) can be biased if the radioligand concentration exceeds “tracer” levels. Negative bias would also arise in successive PET scans if clearance of the radioligand is slow, resulting in a carryover effect. We developed a method to (1) estimate the in vivo dissociation constant Kd of a radioligand from PET studies displaying a non-tracer carryover (NTCO) effect and (2) correct the NTCO bias in occupancy studies taking into account the plasma concentration of the radioligand and its in vivo Kd. This method was applied in a study of healthy human subjects with the histamine H3 receptor radioligand [11C]GSK189254 to measure the PK-occupancy relationship of the H3 antagonist PF-03654746. From three test/retest studies, [11C]GSK189254 Kd was estimated to be 9.5 ± 5.9 pM. Oral administration of 0.1 to 4 mg of PF-03654746 resulted in occupancy estimates of 71%–97% and 30%–93% at 3 and 24 h post-drug, respectively. NTCO correction adjusted the occupancy estimates by 0%–15%. Analysis of the relationship between corrected occupancies and PF-03654746 plasma levels indicated that PF-03654746 can fully occupy H3 binding sites ( ROmax = 100%), and its IC50 was estimated to be 0.144 ± 0.010 ng/mL. The uncorrected IC50 was 26% higher.

Intent-Related Differences in Surface EMG of Maximum Eccentric and Concentric Contractions

2003 ◽  
Vol 19 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Mark D. Grabiner ◽  
Tammy M. Owings
Keyword(s):  
Muscle Activation ◽  
Vastus Lateralis ◽  
Knee Extensor ◽  
Eccentric Contraction ◽  
Surface Emg ◽  
Vastus Lateralis Muscle ◽  
Concentric Contractions ◽  
Concentric Contraction ◽  
Contraction Condition ◽  
The Difference

For this study it was hypothesized that when participants intended to perform a maximum voluntary concentric (or eccentric) contraction but had an eccentric (or concentric) contraction imposed upon them, the initial EMG measured during the isometric phase preceding the onset of the dynamometer motion would reflect the intended contraction condition. The surface EMG of the vastus lateralis muscle was measured in 24 participants performing isokinetic concentric and eccentric maximum voluntary knee extensor contractions. The contractions were initiated from rest and from the same knee flexion angle and required the same level of external force to trigger the onset of dynamometer motion. Vastus lateralis EMG were quantified during the isometric phase preceding the onset of the dynamometer motion. When participants intended to perform a concentric contraction but had an eccentric contraction imposed upon them, the initial EMG resembled that of a concentric contraction. When they intended to perform an eccentric contraction but had a concentric contraction imposed upon them, the initial EMG resembled that of an eccentric contraction. Overall, the difference between concentric and eccentric contractions observed during the period of theinitialmuscle activation implies that descending signals include information that distinguishes between eccentric and concentric contractions.

scholarly journals African plant foods rich in non-starch polysaccharides reduce postprandial blood glucose and insulin concentrations in healthy human subjects

1998 ◽  
Vol 80 (5) ◽  
pp. 419-428 ◽  
Author(s):  
Uchenna A. Onyechi ◽  
Patricia A. Judd ◽  
Peter R. Ellis
Keyword(s):  
Blood Glucose ◽  
Human Subjects ◽  
Physiological Activity ◽  
Venous Blood ◽  
Area Under The Curve ◽  
Water Soluble ◽  
Postprandial Blood Glucose ◽  
Wheat Bread ◽  
Healthy Human ◽  
Time Points

The effects of two vegetable flours, prepared from the African plants Detarium senegalense Gmelin, a legume, and Cissus rotundifolia, a shrub, on postprandial blood glucose and insulin concentrations in human subjects, were investigated. Chemical analysis indicated that these flours contained significant amounts of NSP. The detarium in particular was found to be a rich source of water-soluble NSP (SNSP). The flours were incorporated into two types of breakfast meal, a stew meal and a wheat bread meal, containing 50 g and 70 g available carbohydrate respectively. Both meals also contained 10–12g NSP, the major fraction of which was SNSP. Control and fibre-rich meals were consumed on separate days in randomized order by two different groups of subjects (n 5, stew meals; n 10, bread meals). Venous blood samples were taken at fasting (0 min) and postprandially at 30 min intervals for 2·5 h and the plasma analysed for glucose and insulin. Compared with the controls, detarium and cissus meals elicited significant reductions (P < 0·006) in plasma glucose levels at most postprandial time points and for area-under-the-curve (AUC) values (AUC reductions 38–62%). Significant reductions (P < 0·002) in plasma insulin levels at various postprandial time points and for AUC values were also seen after detarium and cissus breads (AUC reductions 43 and 36% respectively), but not after the fibre-rich stew meals. SNSP and starch are possibly the main, but not the only, components responsible for the glucose- and insulin-lowering effects of cissus flour. The main SNSP fraction of detarium, identified as a high-molecular-weight xyloglucan, is likely to be a primary factor in determining the physiological activity of detarium flour.

Effect of hormonal and substrate backgrounds on cell membrane function in normal males

1987 ◽  
Vol 63 (3) ◽  
pp. 1107-1113 ◽  
Author(s):  
G. A. Fantini ◽  
J. P. Roberts ◽  
S. F. Lowry ◽  
J. D. Albert ◽  
K. J. Tracey ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Vastus Lateralis ◽  
Cellular Membrane ◽  
Resting Membrane Potential ◽  
Vastus Lateralis Muscle ◽  
Epinephrine Infusion ◽  
Membrane Function ◽  
Tibialis Muscle ◽  
Group B

Hormonal and substrate influences on in vivo cellular membrane function were evaluated in 15 healthy male volunteers. Each subject underwent serial evaluations of membrane function in the anterior tibialis muscle, as assessed by transcutaneous measurement of resting membrane potential (Em). Group A subjects (n = 9) underwent measurement of resting Em in the basal state and again during the 10th day of intravenous feeding (IVF). Group B subjects (n = 6) underwent measurement of resting Em in the basal state during epinephrine infusion and again during epinephrine infusion on the 7th day of IVF. Percutaneous needle biopsy of the vastus lateralis muscle permitted calculation of transmembrane electrolyte distribution from the Nernst equation, using the measured Em and the chloride space method. Hospitalization with intake of a defined-formula enteral diet for 3 days resulted in depolarization (P less than 0.05) of resting Em (-75.3 +/- 1.6 mV) compared with normal (-79.8 +/- 0.9 mV). Despite 10 days of subsequent IVF, further depolarization (P less than 0.05) of resting Em (-71.2 +/- 1.2 mV) was observed. In the dual presence of IVF and exogenous epinephrine infusion, there was an increase (P less than 0.05) in intracellular potassium concentration and repolarization of resting Em (-80.6 +/- 0.8 mV) to normal levels. These data indicate that hormonal background and substrate availability contribute to the in vivo modulation of cellular membrane function in human skeletal muscle, possibly through facilitation of sodium-dependent amino acid transport across the cell membrane.

Eccentric exercise markedly increases c-Jun NH2-terminal kinase activity in human skeletal muscle

1999 ◽  
Vol 87 (5) ◽  
pp. 1668-1673 ◽  
Author(s):  
Marni D. Boppart ◽  
Doron Aronson ◽  
Lindsay Gibson ◽  
Ronenn Roubenoff ◽  
Leslie W. Abad ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Eccentric Exercise ◽  
Intracellular Signaling ◽  
Human Skeletal Muscle ◽  
Vastus Lateralis ◽  
Fold Increase ◽  
Mitogen Activated Protein Kinase ◽  
Eccentric Contractions ◽  
Vastus Lateralis Muscle

Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 ± 4.5 vs. 3.5 ± 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle.

scholarly journals In vivo strain of the medial vs. lateral quadriceps tendon in patellofemoral pain syndrome

2009 ◽  
Vol 107 (2) ◽  
pp. 422-428 ◽  
Author(s):  
Nicole A. Wilson ◽  
Joel M. Press ◽  
Li-Qun Zhang
Keyword(s):  
Vastus Lateralis ◽  
Knee Extensor ◽  
Pain Syndrome ◽  
Quadriceps Tendon ◽  
Biomechanical Properties ◽  
Patellofemoral Pain ◽  
Control Subjects ◽  
Patellar Maltracking ◽  
Tendon Strain

Patellofemoral pain (PFP) is thought to be related to patellar maltracking due to imbalances in the knee extensor. However, no study has evaluated the in vivo biomechanical properties of the quadriceps tendon in PFP syndrome. Our purpose was to compare the biomechanical properties of the quadriceps tendons in vivo and noninvasively in patients with PFP syndrome to those of control subjects. The null hypothesis was that the quadriceps tendons of PFP subjects would have significantly decreased strain compared with control subjects. Fourteen subjects (7 control, 7 PFP) performed voluntary ramp isometric contractions to a range of torque levels, while quadriceps tendon elongation was measured using ultrasonography. Tendon strain was calculated for the vastus medialis obliquus (VMO) and vastus lateralis (VL) portion of the quadriceps tendon and compared between subjects (control vs. PFP) and within subjects (VMO vs. VL). PFP subjects showed significantly less VMO tendon strain than control subjects ( P < 0.001), but there was no difference in VL tendon strain between PFP and control subjects ( P = 0.100). Relative weakness of the VMO is the most likely cause of the decreased tendon strain seen in subjects with PFP. VMO weakness not only explains the decreased medial tendon strain but also explains the presence of increased lateral patellar translation and lateral patellar spin (distal pole rotates laterally) reported in the literature in this population. This technique can potentially be used in a clinical setting to evaluate quadriceps tendon properties and infer the presence of muscle weakness in PFP.

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