Effects of acute exercise and training status on glucocorticoid-induced leucine zipper (GILZ) expression in human skeletal muscle.

Interactions between statin therapy and physical exercise complicate effective cardiovascular prevention. Emerging evidence suggests that muscle strain related changes in the expression of the glucocorticoid-induced leucine zipper (GILZ) may be involved. Therefore, we measured GILZ mRNA expression levels in M. vastus lateralis samples of 32 healthy individuals before and after a standardized bout of strength or endurance exercise. Overall, we found a highly significant downregulation of GILZ after exercise training (p < 0.001). Within-subgroup changes were statistically significant only after strength training, supporting the role of muscle (as opposed to cardiocirculatory) strain. If confirmed, this may help fitting training recommendations and medication.

Assessment of myocardial function and cardiac performance using left ventricular global longitudinal strain in athletes after COVID-19: a follow-up study.

Background: It has not yet been conclusively determined whether reduced left ventricular global longitudinal strain (LV GLS) after COVID-19 contributes to a reduction in exercise capacity. Our own studies showed a possible mild myocardial involvement in the form of reduced LV GLS in athletes after COVID-19 compared with healthy athletes. The aims of this prospective follow-up study were to investigate the development of LV GLS over a 3-month period in athletes after COVID-19 and the possible relationship between LV GLS and physical performance. Methods: LV GLS was determined in four-, two-, and three-chamber views and assessed offline by a blinded investigator in 96 recreational athletes (mean age 33.15 ± 12.40 years, 53 male, peak VO2 38.82 ± 11.14 ml/min/kg) at a median of two (t0) and five months (t1) after COVID-19. Cardiopulmonary exercise testing (CPET) was performed on a bicycle ergometer on both examination dates. Results: LV GLS improved significantly between t0 and t1 (t0 -18.82 ± 2.02 vs. t1 -19.46 ± 2.05, p < 0.001). Echocardiographic and spiroergometric parameters were within the normal clinical reference range. Maximum power increased significantly from t0 to t1 (t0 283.17 ± 83.20 vs. t1 286.24 ± 85.22 Watt, p = 0.009) and there was a trend toward increased peak oxygen uptake (t0 36.82 ± 11.14 vs. t1 38.68 ± 10.26 ml/min/kg, p = 0.069). We found no correlation between LV GLS and performance parameters, except for the respiratory exchange ratio (RER) [ρ -0.316, (-0.501; -0.102), p < 0.050]. Conclusions: Significant improvement in LV GLS approximately five months after COVID-19 may be due to mild myocardial involvement during or shortly after COVID-19, which seems to recover. There was no correlation between LV GLS and performance parameters, except for an inverse correlation of LV GLS and RER, suggesting insufficient exercise intolerance at lower GLS values. Further studies on the development of GLS in athletes or in the general population with moderate and severe disease courses would be informative as well as the comparison of pre-COVID-19 with post-COVID-19 echocardiography to evaluate the effects of COVID-19 on cardiac function.

Testing anabolic activity, potency and mechanisms of action of the phyto-derived beta 2 agonist higenamine.

Higenamine (Hige), a plant derived alkaloid is classified as ß2 agonist by the World Anti-Doping Agency (WADA). However, pharmacologic mechanisms of its performance-enhancing activity have not been investigated so far. Therefore, we investigate the anabolic activity and associated molecular mechanisms of Hige in C2C12 myotubes. In differentiated C2C12 cells dose-dependent effects of Hige on myotube size were analyzed. The mRNA expression of genes involved in hypertrophy was measured. For mechanistic studies, ß2-adrenoceptor (ADRB2), androgen receptor (AR), and estrogen receptor (ER) inhibitors and dexamethasone (Dexa) were co-incubated and myotube diameter was evaluated. The interaction of Hige with the AR and ER was investigated. Hige treatment significantly increased myotube diameters and stimulated the mRNA expression of hypertrophy-involved genes. In contrast to the ADRB2 inhibitor (ICI 118551), the ER inhibitor ZK 191703, the AR inhibitor Flutamide (Flu), and treatment with Dexa were able to antagonize the Hige-induced increase of myotube diameter. Hige has antagonistic activity in the AR and ER yeast transactivation assay. Our results demonstrate that Hige induces anabolic effects in C2C12 cells but not via the ADRB2. There are indications for a cross talk between Hige and the AR and ER. Future studies are necessary to investigate the involved molecular mechanisms.

Combinatory in vitro effects of the ß2-agonists salbutamol and formoterol in skeletal muscle cells.

ß2-agonists are used for the treatment of bronchoconstriction, but also abused in doping. Beside an ergogenic activity ß2-agonists may have also anabolic activity. Therefore, we investigated the anabolic activity and associated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) alone, as well as in combination in C2C12 myotubes. In differentiated C2C12 cells, dose-dependent effects of SAL and FOR (alone/in combination) on myotube diameter, myosin heavy chain (MHC) protein expression and the mRNA expression of genes involved in hypertrophy were analyzed. ß2-adrenoceptor 2 (ADRB2), androgen receptor (AR) and estrogen receptor (ER) inhibitors, as well as dexamethasone (Dexa) were co-incubated with the ß2-agonists and myotube diameter was determined. SAL and FOR treatment significantly induced hypertrophy and increased MHC expression and the mRNA expression of Igf1, mTOR, PIk3r1 and AMpKa2. In contrast to an ER inhibitor, the ADRB2 and AR inhibitors, as well as Dexa antagonized FOR and SAL induced hypertrophy. Combined treatment with SAL and FOR resulted in significant additive effects on myotube diameter and MHC expression. Future clinical studies are needed to prove this effect in humans and to evaluate this finding with respect to antidoping regulations.

Endurance training alters enzymatic and rheological properties of red blood cells (RBC) in type 2 diabetic men during in vivo RBC aging.

This study examines the effects of endurance training on red blood cells (RBC) in seventeen non-insulin-dependent type 2 diabetic men with a special focus on in vivo RBC aging. Venous blood was collected pre- and post-training at rest. RBC from whole blood and RBC separated according to cell age by density-gradient centrifugation were analyzed. RBC deformability was measured by ektacytometry. Immunohistochemical staining was performed to quantify the RBC-nitric oxide (NO) synthase activation (RBC-NOSSer1177) because RBC-NOS-produced NO can contribute to increased RBC deformability. The proportion of "young" RBC was significantly higher post-training. RBC deformability of all RBC (RBC of all ages) remained unaltered post-training. During RBC aging, RBC deformability decreased in both pre- and post-training. However, the training significantly increased RBC deformability in "young" and reduced their deformability in aging RBC. RBC-NOS activation remained unaltered in all RBC post-training. It tendentially increased in aging RBC pre-training, but did not change during aging post-training. The training significantly reduced RBC-NOS activation in "old" RBC. Endurance training may improve the RBC system (higher amount of "young" RBC which are more deformable). It remains speculative whether changes in older RBC (reduced RBC-NOS activation and deformability) could lead to more rapid elimination of aged RBC.