Now showing 1 - 10 of 13
  • Publication
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    Resistance training does not increase myocellular garbage dumps: A pilot study on lipofuscin in skeletal muscle fibers of resistance trained young men
    (2024-01-31)
    Jacko, Daniel 
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    Masur, Lukas 
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    Schaaf, Kirill 
    ;
    Zacher, Jonas 
    ;
    ;
    Marées, Markus de 
    ;
    Bloch, Wilhelm 
    ;
    Lipofuscin (LF) is an intracellular aggregate associated with proteostatic impairments, especially prevalent in nondividing skeletal muscle fibers. Reactive oxygen species (ROS) drive LF-formation. Resistance training (RT) improves muscle performance but also increases ROS production, potentially promoting LF-formation. Thus, we aimed to investigate if RT of a mesocycle duration increases LF-formation in type-I and II muscle fibers and whether RT increases the antioxidant capacity (AOC) in terms of SOD1 and SOD2 content. An intervention group (IG) performed 14 eccentrically accented RT-sessions within 7 weeks. Vastus lateralis muscle biopsies were collected before and after the intervention from IG as well as from a control group (CG) which refrained from RT for the same duration. LF was predominantly found near nuclei, followed by membrane-near and a minor amount in the fiber core, with corresponding spot sizes. Overall, LF-content was higher in type-I than type-II fibers (p < 0.05). There was no increase in LF-content in type-I or IIA fibers, neither for the IG following RT nor for the CG. The same is valid for SOD1/2. We conclude that, in healthy subjects, RT can be safely performed, without adverse effects on increased LF-formation.
      7
  • Publication
    Metadata only
    Enhanced capacity for CaMKII signaling mitigates calcium release related contractile fatigue with high intensity exercise
    (2023)
    Flück, Martin 
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    Sanchez, Colline 
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    Jacquemond, Vincent 
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    Berthier, Christine 
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    Giraud, Marie-Noëlle 
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    Jacko, Daniel 
    ;
    ; ;
    Baan, Guus 
    ;
    Jaspers, Richard T. 
      5
  • Publication
    Metadata only
    Resistance exercise: a mighty tool that adapts, destroys, rebuilds and modulates the molecular and structural environment of skeletal muscle
    (2023) ;
    So-Young, Park 
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    Schaaf, Kirill 
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    Yang, Woo-Hwi 
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    Theis, Christian 
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    Jacko, Daniel 
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    Purpose: Skeletal muscle regulates health and performance by maintaining or increasing strength and muscle mass. Although the molecular mechanisms in response to resistance exercise (RE) significantly target the activation of protein synthesis, a plethora of other mechanisms and structures must be involved in orchestrating the communication, repair, and restoration of homeostasis after RE stimulation. In practice, RE can be modulated by variations in intensity, continuity and volume, which affect molecular responses and skeletal muscle adaptation. Knowledge of these aspects is important with respect to planning of training programs and assessing the impact of RE training on skeletal muscle. Methods: In this narrative review, we introduce general aspects of skeletal muscle substructures that adapt in response to RE. We further highlighted the molecular mechanisms that control human skeletal muscle anabolism, degradation, repair and memory in response to acute and repeated RE and linked these aspects to major training variables. Results: Although RE is a key stimulus for the activation of skeletal muscle anabolism, it also induces myofibrillar damage. Nevertheless, to increase muscle mass accompanied by a corresponding adaptation of the essential substructures of the sarcomeric environment, RE must be continuously repeated. This requires the permanent engagement of molecular mechanisms that re-establish skeletal muscle integrity after each RE-induced muscle damage. Conclusion: Various molecular regulators coordinately control the adaptation of skeletal muscle after acute and repeated RE and expand their actions far beyond muscle growth. Variations of key resistance training variables likely affect these mechanisms without affecting muscle growth. Keywords: adaptation; hypertrophy; mTOR signaling; muscle damage; proteostasis; resistance exercise; skeletal muscle.
      5
  • Publication
    Metadata only
    Repeated and Interrupted Resistance Exercise Induces the Desensitization and Re-Sensitization of mTOR-Related Signaling in Human Skeletal Muscle Fibers.
    (2022-05-12)
    Jacko, Daniel 
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    Schaaf, Kirill 
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    Masur, Lukas 
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    Windoffer, Hannes 
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    Aussieker, Thorben 
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    Schiffer, Thorsten 
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    Zacher, Jonas 
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    Bloch, Wilhelm 
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    The acute resistance exercise (RE)-induced phosphorylation of mTOR-related signaling proteins in skeletal muscle can be blunted after repeated RE. The time frame in which the phosphorylation (p) of mTORS2448, p70S6kT421/S424, and rpS6S235/236 will be reduced during an RE training period in humans and whether progressive (PR) loading can counteract such a decline has not been described. (1) To enclose the time frame in which pmTORS2448, prpS6S235/236, and pp70S6kT421/S424 are acutely reduced after RE occurs during repeated RE. (2) To test whether PR will prevent that reduction compared to constant loading (CO) and (3) whether 10 days without RE may re-increase blunted signaling. Fourteen healthy males (24 ± 2.8 yrs.; 1.83 ± 0.1 cm; 79.3 ± 8.5 kg) were subjected to RE with either PR (n = 8) or CO (n = 6) loading. Subjects performed RE thrice per week, conducting three sets with 10–12 repetitions on a leg press and leg extension machine. Muscle biopsies were collected at rest (T0), 45 min after the first (T1), seventh (T7), 13th (T13), and 14th (X-T14) RE session. No differences were found between PR and CO for any parameter. Thus, the groups were combined, and the results show the merged values. prpS6S235/236 and pp70s6kT421/S424 were increased at T1, but were already reduced at T7 and up to T13 compared to T1. Ten days without RE re-increased prpS6S235/236 and pp70S6kT421/S424 at X-T14 to a level comparable to that of T1. pmTORS2448 was increased from T1 to X-T14 and did not decline over the training period. Single-fiber immunohistochemistry revealed a reduction in prpS6S235/236 in type I fibers from T1 to T13 and a re-increase at X-T14, which was more augmented in type II fibers at T13 (p < 0.05). The entity of myofibers revealed a high heterogeneity in the level of prpS6S235/236, possibly reflecting individual contraction-induced stress during RE. The type I and II myofiber diameter increased from T0 and T1 to T13 and X-T14 (p < 0.05) prpS6S235/236 and pp70s6kT421/S424 reflect RE-induced states of desensitization and re-sensitization in dependency on frequent loading by RE, but also by its cessation.
      9
  • Publication
    Metadata only
    Coordinated alpha-crystallin B phosphorylation and desmin expression indicate adaptation and deadaptation to resistance exercise-induced loading in human skeletal muscle
    (2020)
    Jacko, Daniel 
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    Bersinger, Käthe 
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    Schulz, Oliver 
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    Przyklenk, Axel 
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    Spahiu, Fabian 
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    Höhfeld, Jörg 
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    Bloch, Wilhelm 
    ;
    Skeletal muscle is a target of contraction-induced loading (CiL), leading to protein unfolding or cellular perturbations, respectively. While cytoskeletal desmin is responsible for ongoing structural stabilization, in the immediate response to CiL, alpha-crystallin B (CRYAB) is phosphorylated at serine 59 (pCRYABS59) by P38, acutely protecting the cytoskeleton. To reveal adaptation and deadaptation of these myofibrillar subsystems to CiL, we examined CRYAB, P38, and desmin regulation following resistance exercise at diverse time points of a chronic training period. Mechanosensitive JNK phosphorylation (pJNKT183/Y185) was determined to indicate the presence of mechanical components in CiL. Within 6 wk, subjects performed 13 resistance exercise bouts at the 8–12 repetition maximum, followed by 10 days detraining and a final 14th bout. Biopsies were taken at baseline and after the 1st, 3rd, 7th, 10th, 13th, and 14th bout. To assess whether potential desensitization to CiL can be mitigated, one group trained with progressive and a second with constant loading. As no group differences were found, all subjects were combined for statistics. Total and phosphorylated P38 was not regulated over the time course. pCRYABS59 and pJNKT183/Y185 strongly increased following the unaccustomed first bout. This exercise-induced pCRYABS59/pJNKT183/Y185 increase disappeared with the 10th until 13th bout. As response to the detraining period, the 14th bout led to a renewed increase in pCRYABS59. Desmin content followed pCRYABS59 inversely, i.e., was up- when pCRYABS59 was downregulated and vice versa. In conclusion, the pCRYABS59 response indicates increase and decrease in resistance to CiL, in which a reinforced desmin network could play an essential role by structurally stabilizing the cells.
      3
  • Publication
    Metadata only
    PKM2 Determines Myofiber Hypertrophy In Vitro and Increases in Response to Resistance Exercise in Human Skeletal Muscle
    (2020)
    Verbrugge, Sander 
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    Stadhouders, Lian 
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    Jacko, Daniel 
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    Aussieker, Thorben 
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    M J de Wit, Gerard 
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    Vogel, Ilse 
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    Offringa, Carla 
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    Schönfelder, Martin 
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    Jaspers, Richard 
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    Wackerhage, Henning 
    Nearly 100 years ago, Otto Warburg investigated the metabolism of growing tissues and discovered that tumors reprogram their metabolism. It is poorly understood whether and how hypertrophying muscle, another growing tissue, reprograms its metabolism too. Here, we studied pyruvate kinase muscle (PKM), which can be spliced into two isoforms (PKM1, PKM2). This is of interest, because PKM2 redirects glycolytic flux towards biosynthetic pathways, which might contribute to muscle hypertrophy too. We first investigated whether resistance exercise changes PKM isoform expression in growing human skeletal muscle and found that PKM2 abundance increases after six weeks of resistance training, whereas PKM1 decreases. Second, we determined that Pkm2 expression is higher in fast compared to slow fiber types in rat skeletal muscle. Third, by inducing hypertrophy in differentiated C2C12 cells and by selectively silencing Pkm1 and/or Pkm2 with siRNA, we found that PKM2 limits myotube growth. We conclude that PKM2 contributes to hypertrophy in C2C12 myotubes and indicates a changed metabolic environment within hypertrophying human skeletal muscle fibers. PKM2 is preferentially expressed in fast muscle fibers and may partly contribute to the increased potential for hypertrophy in fast fibers.
      4
  • Publication
    Metadata only
    Coordinated alpha-crystallin B phosphorylation and desmin expression indicate adaptation and deadaptation to resistance exercise-induced loading in human skeletal muscle
    (2020)
    Jacko, Daniel 
    ;
    ;
    Schulz, Oliver 
    ;
    Przyklenk, Axel 
    ;
    Spahiu, Fabian 
    ;
    Höhfeld, Jörg 
    ;
    Bloch, Wilhelm 
    ;
    Skeletal muscle is a target of contraction-induced loading (CiL), leading to protein unfolding or cellular perturbations, respectively. While cytoskeletal desmin is responsible for ongoing structural stabilization, in the immediate response to CiL, alpha-crystallin B (CRYAB) is phosphorylated at serine 59 (pCRYABS59) by P38, acutely protecting the cytoskeleton. To reveal adaptation and deadaptation of these myofibrillar subsystems to CiL, we examined CRYAB, P38, and desmin regulation following resistance exercise at diverse time points of a chronic training period. Mechanosensitive JNK phosphorylation (pJNKT183/Y185) was determined to indicate the presence of mechanical components in CiL. Within 6 wk, subjects performed 13 resistance exercise bouts at the 8-12 repetition maximum, followed by 10 days detraining and a final 14th bout. Biopsies were taken at baseline and after the 1st, 3rd, 7th, 10th, 13th, and 14th bout. To assess whether potential desensitization to CiL can be mitigated, one group trained with progressive and a second with constant loading. As no group differences were found, all subjects were combined for statistics. Total and phosphorylated P38 was not regulated over the time course. pCRYABS59 and pJNKT183/Y185 strongly increased following the unaccustomed first bout. This exercise-induced pCRYABS59/pJNKT183/Y185 increase disappeared with the 10th until 13th bout. As response to the detraining period, the 14th bout led to a renewed increase in pCRYABS59. Desmin content followed pCRYABS59 inversely, i.e., was up- when pCRYABS59 was downregulated and vice versa. In conclusion, the pCRYABS59 response indicates increase and decrease in resistance to CiL, in which a reinforced desmin network could play an essential role by structurally stabilizing the cells.
      4
  • Publication
    Metadata only
      2
  • Publication
    Metadata only
    Phosphorylation of αB-crystallin and its cytoskeleton association differs in skeletal myofiber types depending on resistance exercise intensity and volume
    (2019)
    Jacko, Daniel 
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    ;
    Hebchen, Jonas 
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    Marées, Markus 
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    Bloch, Wilhelm 
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    αB-crystallin (CRYAB) is an important actor in the immediate cell stabilizing response following mechanical stress in skeletal muscle. Yet, only little is known regarding myofiber type-specific stress responses of CRYAB. We investigated whether the phosphorylation of CRYAB at serine 59 (pCRYABSer59) and its cytoskeleton association are influenced by varying load-intensity and -volume in a fiber type-specific manner. Male subjects were assigned to 1, 5, and 10 sets of different acute resistance exercise protocols: hypertrophy (HYP), maximum strength (MAX), strength endurance (SE), low intensity (LI), and three sets of maximum eccentric resistance exercise (ECC). Skeletal muscle biopsies were taken at baseline and 30 min after exercise. Western blot revealed an increase in pCRYABSer59 only following 5 and 10 sets in groups HYP, MAX, SE, and LI as well as following 3 sets in the ECC group. In type I fibers, immunohistochemistry determined increased pCRYABSer59 in all groups. In type II fibers, pCRYABSer59 only increased in MAX and ECC groups, with the increase in type II fibers exceeding that of type I fibers in ECC. Association of CRYAB and pCRYABSer59 with the cytoskeleton reflected the fiber type-specific phosphorylation pattern. Phosphorylation of CRYAB and its association with the cytoskeleton in type I and II myofibers is highly specific in terms of loading intensity and volume. Most likely, this is based on specific recruitment patterns of the different myofiber entities due to the different resistance exercise loadings. We conclude that pCRYABSer59 indicates contraction-induced mechanical stress exposure of single myofibers in consequence of resistance exercise. NEW & NOTEWORTHY We determined that the phosphorylation of αB-crystallin at serine 59 (pCRYABSer59) after resistance exercise differs between myofiber types in a load- and intensity-dependent manner. The determination of pCRYABSer59 could serve as a marker indirectly indicating contractile involvement and applied mechanical stress on individual fibers. By that, it is possible to retrospectively assess the impact of resistance exercise loading on skeletal muscle fiber entities.
      4
  • Publication
    Metadata only
    Resistance exercise-induced muscle fatigue is not accompanied by increased phosphorylation of ryanodine receptor 1 at serine 2843
    (2018)
    Jacko, Daniel 
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    Friederichs, Gerrit 
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    Ritter, Patrick 
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    Nirenberg, Linnea 
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    Eisenbraun, Jan 
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    de Marées, Markus 
    ;
    Bloch, Wilhelm 
    ;
      2