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| 2. |
- Tonkonogi, Michail, et al.
(författare)
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Endurance training increases stimulation of uncoupling of skeletal muscle mitochondria in humans by non-esterified fatty acids: an uncoupling-protein-mediated effect?
- 2000
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 351:3, s. 805-810
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Tidskriftsartikel (refereegranskat)abstract
- Uncoupled respiration (UCR) is an essential property of muscle mitochondria and has several functions in the cell. We hypothesized that endurance training may alter the magnitude and properties of UCR in human muscle. Isolated mitochondria from muscle biopsies taken before and after 6 weeks of endurance exercise training (n = 8) were analysed for UCR. To investigate the role of uncoupling protein 2 (UCP2) and UCP3 in UCR, the sensitivity of UCR to UCP-regulating ligands (non-esterified fatty acids and purine nucleotides) and UCP2 and UCP3 mRNA expression in muscle were examined. Oleate increased the mitochondrial oxygen consumption rate, an effect that was not attenuated by GDP and/or cyclosporin A. The effect of oleate was significantly greater after compared with before training. Training had no effect on UCP2 or UCP3 mRNA levels, but after training the relative increase in respiration rate induced by oleate was positively correlated with the UCP2 mRNA level. In conclusion, we show that the sensitivity of UCR to non-esterified fatty acids is up-regulated by endurance training. This suggests that endurance training causes intrinsic changes in mitochondrial function, which may enhance the potential for regulation of aerobic energy production, prevent excess free radical generation and contribute to a higher basal metabolic rate.
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| 3. |
- Tonkonogi, Michail, et al.
(författare)
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Mitochondrial function in human skeletal muscle is not impaired by high intensity exercise.
- 1999
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 437:4, s. 562-8
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that high-intensity (HI) intermittent exercise impairs mitochondrial function was investigated with different microtechniques in human muscle samples. Ten male students performed three bouts of cycling at 130% of peak O2 consumption (V.O2,peak). Muscle biopsies were taken from the vastus lateralis muscle at rest, at fatigue and after 110 min recovery. Mitochondrial function was measured both in isolated mitochondria and in muscle fibre bundles made permeable with saponin (skinned fibres). In isolated mitochondria there was no change in maximal respiration, rate of adenosine 5'-triphosphate (ATP) production (measured with bioluminescence) and respiratory control index after exercise or after recovery. The ATP production per consumed oxygen (P/O ratio) also remained unchanged at fatigue but decreased by 4% (P<0.05) after recovery. In skinned fibres, maximal adenosine 5'-diphosphate (ADP)-stimulated respiration increased by 23% from rest to exhaustion (P<0.05) and remained elevated after recovery, whereas the respiratory rates in the absence of ADP and at 0.1 mM ADP (submaximal respiration) were unchanged. The ratio between respiration at 0.1 and 1 mM ADP (ADP sensitivity index) decreased at fatigue (P<0.05) but after the recovery period was not significantly different from that at rest. It is concluded that mitochondrial oxidative potential is maintained or improved during exhaustive HI exercise. The finding that the sensitivity of mitochondrial respiration to ADP is reversibly decreased after strenuous exercise may indicate that the control of mitochondrial respiration is altered.
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| 4. |
- Tonkonogi, Michail, et al.
(författare)
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Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans.
- 2003
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 446:2, s. 261-9
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that the aging process is associated with mitochondrial dysfunction and oxidative stress has been investigated in human skeletal muscle. Muscle biopsy samples were taken from seven old male subjects [OS; 75 (range 61-86) years] and eight young male subjects [YS; 25 (22-31) years]. Oxidative function was measured both in permeabilised muscle fibres and isolated mitochondria. Despite matching the degree of physical activity, OS had a lower training status than YS as judged from pulmonary maximal O(2) consumption ( Vdot;O(2)max, -36%) and handgrip strength (-20%). Both maximal respiration and creatine-stimulated respiration were reduced in muscle fibres from OS (-32 and -34%, respectively). In contrast, respiration in isolated mitochondria was similar in OS and YS. The discrepancy might be explained by a biased harvest of "healthy" mitochondria and/or disruption of structural components during the process of isolation. Cytochrome C oxidase was reduced (-40%, P<0.01), whereas UCP3 protein tended to be elevated in OS ( P=0.09). Generation of reactive oxygen species by isolated mitochondria and measures of antioxidative defence (muscle content of glutathione, glutathione redox status, antioxidative enzymes activity) were not significantly different between OS and YS. It is concluded that aging is associated with mitochondrial dysfunction, which appears to be unrelated to reduced physical activity. The hypothesis of increased oxidative stress in aged muscle could not be confirmed in this study.
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| 5. |
- Tonkonogi, Michail, et al.
(författare)
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The role of phosphorylcreatine in the regulation of mitochondrial respiration in human skeletal muscle.
- 2001
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Ingår i: Journal of Physiology. - 0022-3751 .- 1469-7793. ; 537:3, s. 971-978
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Tidskriftsartikel (refereegranskat)abstract
- 1. The role of phosphorylcreatine (PCr) and creatine (Cr) in the regulation of mitochondrial respiration was investigated in permeabilised fibre bundles prepared from human vastus lateralis muscle. 2. Fibre respiration was measured in the absence of ADP (V0) and after sequential additions of submaximal ADP (0.1 mm ADP, Vsubmax), PCr (or Cr) and saturating [ADP] (Vmax). 3. Vsubmax increased by 55% after addition of saturating creatine (P< 0.01; n = 8) and half the maximal effect was obtained at 5 mm [Cr]. In contrast, Vsubmax decreased by 54% after addition of saturating phosphorylcreatine (P< 0.01; n = 8) and half the maximal effect was obtained at 1 mm [PCr]. Vmax was not affected by Cr or PCr. 4. Vsubmax was similar when PCr and Cr were added simultaneously at concentrations similar to those in muscle at rest (PCr/Cr = 2) and at low-intensity exercise (PCr/Cr = 0.5). At conditions mimicking high-intensity exercise (PCr/Cr = 0.1), Vsubmax increased to 60% of Vmax (P< 0.01) vs. rest and low-intensity exercise). 5. Eight of the subjects participated in a 16 day Cr supplementation programme. Following Cr supplementation, V0 decreased by 17% (P< 0.01) vs. prior to Cr supplementation), whereas ADP-stimulated respiration (with and without Cr or PCr) was unchanged. 6. For the first time evidence is given that PCr is an important regulator of mitochondrial ADP-stimulated respiration. Phosphorylcreatine decreases the sensitivity of mitochondrial respiration to ADP whereas Cr has the opposite effect. During transition from rest to high-intensity exercise, decreases in the PCr/Cr ratio will effectively increase the sensitivity of mitochondrial respiration to ADP. The decrease in V0 after Cr supplementation indicates that intrinsic changes in membrane proton conductance occur.
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| 6. |
- Walsh, Brandon, et al.
(författare)
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Effect of eccentric exercise on muscle oxidative function in man.
- 2001
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 33:3, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to evaluate the effects of eccentric exercise on muscle oxidative function. Methods: Thirteen subjects performed high-intensity eccentric cycling for 30 min. Muscle oxidative function in vastus lateralis was evaluated by measurements of respiration in permeabilized muscle fibers (skinned fibers) and from the kinetics of oxyhemoglobin (oxyHb) saturation measured with near infrared spectroscopy (NIRS). Results: After eccentric cycling, all subjects reported extensive delayed onset muscle soreness (DOMS), but plasma markers of muscle damage (creatine kinase and [beta]-glucuronidase activity) were not significantly altered. The half time of oxyHb desaturation after circulatory occlusion (128 +/- 11 s, mean +/- SE) and oxyHb resaturation after restoration of blood flow (13.8 +/- 0.7 s) were not significantly changed after eccentric cycling (N = 7). Respiration in skinned muscle fibers measured in the absence of ADP and in the presence of a submaximal (0.1 mM) or maximal ADP concentration (1 mM) was not significantly changed after eccentric cycling (N = 6). The sensitivity of respiration to ADP was not significantly changed after eccentric cycling. Conclusions: Muscle oxidative function (maximal respiration and respiratory control by ADP) was not compromised after high-intensity eccentric cycle exercise. Furthermore, NIRS indicates that after eccentric cycling muscle oxygen utilization and local oxygen transport at rest are unchanged. It is concluded that eccentric cycling, although causing DOMS, does not negatively affect skeletal muscle oxidative function.
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| 7. |
- Walsh, Brandon, et al.
(författare)
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Increased concentrations of Pi and lactic acid reduce creatine stimulated respiration in muscle fibres.
- 2002
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 92, s. 2273-2276
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that the respiratory function of skeletal muscle mitochondria is impaired by lactic acidosis and elevated concentrations of Pi. The rate of respiration of chemically skinned fiber bundles from rat soleus muscle was measured at [Pi] (brackets denote concentration) and pH values similar to those at rest (3 mM Pi, pH 7.0) and high-intensity exercise (20 mM Pi, pH 6.6). Respiration was measured in the absence of ADP and after sequential additions of 0.1 mM ADP, 20 mM creatine (Cr; VCr), and 4 mM ADP. Respiration at 0.1 mM ADP increased after addition of Cr. However, VCr was 23% lower (P < 0.05) during high-intensity conditions than during resting conditions. VCr was also reduced when Pi or H+ was increased separately (P < 0.05). Respiration in the absence of ADP and after additions of 0.1 mM ADP and 4 mM ADP was not affected by changes in [Pi] or [H+]. The response was similar, irrespective of when acidosis was induced (i.e., quiescent or actively respiring mitochondria). In conclusion, Cr-stimulated respiration is impaired by increases in [H+] and [Pi] corresponding to those in exercising muscle. Although the reduced Cr-stimulated respiration could be compensated for by increased [ADP], this might have implications for intracellular homeostasis.
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| 8. |
- Walsh, Brandon
(författare)
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The role of exercise and exercise-related factors in the control of mitochondrial oxidative function
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The effects of exercise and exercise-related factors on the control of mitochondrial oxidative function were investigated in human and rat skeletal muscle. Oxidative function was assessed through the measurement of oxygen consumption in chemically permeabilized (skinned) fibers. Mitochondria in skinned muscle fibers remain in their natural structural environment, permitting sophisticated mechanisms of respiratory control to be studied while allowing the surrounding milieu to be manipulated. Specifically, the acute effects of eccentric and high intensity exercise, the chronic effects of exercise training, and the role of phosphocreatine (PCr), creatine (Cr), inorganic phosphate (Pi), and H+ in the control mitochondrial oxidative function were studied. Two potentially important metabolites that undergo large changes in concentration in the intracellular milieu during exercise are Cr and PCr. While the importance of these metabolites for temporal energy buffering has long been understood, they also have been suggested to play a role in spatial energy buffering and in the regulation of mitochondrial function in vivo. It is known that Cr, in the presence of submaximally stimulating concentrations of ADP, stimulates respiration in skinned fibers from oxidative muscle. However, the effect of PCr on oxidative function is unknown. It was shown for the first time that PCr decreases the sensitivity of mitochondrial respiration to ADP in skeletal muscle. Additionally, the role of in vivo concentrations of PCr + Cr in respiratory control was demonstrated. The rate of submaximally ADP-stimulated respiration increased two fold when the concentrations of PCr + Cr were increased from those occurring in vivo at rest to those occurring during high intensity (HI) exercise. During HI exercise [Pi] and [H+] can be increased several fold in the intracellular milieu. Although these metabolites play an integral role in oxidative metabolism, it has also been suggested that, in high concentration, they can negatively affect mitochondrial function. Therefore, the effect of these metabolites on respiration in skeletal muscle skinned fibers was investigated. It was shown that increased concentrations of Pi and W, either independently or in combination, decrease the stimulatory effect of Cr on mitochondrial respiration. Although these metabolites inhibit the control of respiration by PCr/Cr, they did not affect maximally ADP-stimulated respiration (Vmax). In order to study the effects of exercise on mitochondrial function, respiratory measurements in skinned fibers were performed in an identical medium prior to and following several types of physical activity. HI exercise (3 bouts of cycling until fatigue at 130% of V02 max) caused a transient decrease in the sensitivity of mitochondrial respiration to ADP. In contrast to previous studies in horse, where Vmax decreased following HI exercise, the maximal respiratory capacity of skeletal muscle increased immediately following HI exercise and remained elevated after 110 min recovery. Eccentric exercise (EE) has been shown to cause structural damage and functional impairment in muscle and has been suggested to deteriorate mitochondrial function. To test this hypothesis, the effect of 30 min of eccentric cycling on skeletal muscle oxidative function was studied. The results demonstrate that EE, despite causing a high degree of delayed onset muscle soreness, does not alter mitochondrial function. It is well known that endurance training results in an up-regulation of both oxygen transport capacity and peripheral oxidative potential. In order to determine more precisely the qualitative and quantitative effects of endurance training on skeletal muscle oxidative function, mitochondrial function was assessed in skinned muscle fibers before and after six weeks of cycle training. After the training period, the rates of non-coupled and maximally ADP-stimulated respiration were increased by roughly 40%, whereas the sensitivity of the individual mitochondrion to ADP decreased. It is concluded that, in addition to increases in mitochondrial density, important qualitative changes in the control of mitochondrial oxidation function occur following endurance training. This dissertation has explained an important mechanism of mitochondrial respiratory control in skeletal muscle by PCr/Cr and demonstrated an inhibition of this mechanism by Pi and H+. Additionally, it was shown that mitochondrial function remains intact or is increased following HI concentric or eccentric exercise. Following endurance training, the sensitivity of the mitochondrion to ADP is decreased whereas the total oxidative capacity of skeletal muscle is increased.
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