Now showing 1 - 6 of 6
- PublicationMetadata onlyResistance training does not increase myocellular garbage dumps: A pilot study on lipofuscin in skeletal muscle fibers of resistance trained young menLipofuscin (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.
- PublicationMetadata onlyIncreased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis(2024)
;Salzmann, Rebekka J.S. ;Krötz, Christina ;Mocan, Tudor ;Mocan, Lavinia P. ;Grapa, Cristiana ;Rottmann, Sophia ;Reichelt, Ramona ;Keller, Cindy M. ;Langhans, Bettina ; ; ; ; ;Krawczyk, Marcin ;Milkiewicz, Piotr ;Sparchez, Zeno ;Lammert, Frank ; ;Gonzalez-Carmona, Maria A. ;Willms, Arnulf ;Strassburg, Christian P. ;Kornek, Miroslaw T. ;Dold, LeonaLukacs-Kornek, VeronikaBackground: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, β and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. Conclusions: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC. 37
- PublicationMetadata onlyResistance exercise: a mighty tool that adapts, destroys, rebuilds and modulates the molecular and structural environment of skeletal musclePurpose: 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.
- PublicationMetadata onlyEnhanced capacity for CaMKII signaling mitigates calcium release related contractile fatigue with high intensity exercise
- PublicationMetadata onlyThe Impact of Vegan and Vegetarian Diets on Physical Performance and Molecular Signaling in Skeletal MuscleMuscular adaptations can be triggered by exercise and diet. As vegan and vegetarian diets differ in nutrient composition compared to an omnivorous diet, a change in dietary regimen might alter physiological responses to physical exercise and influence physical performance. Mitochondria abundance, muscle capillary density, hemoglobin concentration, endothelial function, functional heart morphology and availability of carbohydrates affect endurance performance and can be influenced by diet. Based on these factors, a vegan and vegetarian diet possesses potentially advantageous properties for endurance performance. Properties of the contractile elements, muscle protein synthesis, the neuromuscular system and phosphagen availability affect strength performance and can also be influenced by diet. However, a vegan and vegetarian diet possesses potentially disadvantageous properties for strength performance. Current research has failed to demonstrate consistent differences of performance between diets but a trend towards improved performance after vegetarian and vegan diets for both endurance and strength exercise has been shown. Importantly, diet alters molecular signaling via leucine, creatine, DHA and EPA that directly modulates skeletal muscle adaptation. By changing the gut microbiome, diet can modulate signaling through the production of SFCA.
- PublicationMetadata onlyCoordinated alpha-crystallin B phosphorylation and desmin expression indicate adaptation and deadaptation to resistance exercise-induced loading in human skeletal muscleSkeletal 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.