| 1. |
- Wyckelsma, VL, et al.
(författare)
-
Vitamin C and E Treatment Blocks Changes in Kynurenine Metabolism Triggered by Three Weeks of Sprint Interval Training in Recreationally Active Elderly Humans
- 2021
-
Ingår i: Antioxidants (Basel, Switzerland). - : MDPI AG. - 2076-3921. ; 10:9
-
Tidskriftsartikel (refereegranskat)abstract
- The kynurenine pathway (KP) is gaining attention in several clinical fields. Recent studies show that physical exercise offers a therapeutic way to improve ratios of neurotoxic to neuroprotective KP metabolites. Antioxidant supplementation can blunt beneficial responses to physical exercise. We here studied the effects of endurance training in the form of sprint interval training (SIT; three sessions of 4–6 × 30 s cycling sprints per week for three weeks) in elderly (~65 years) men exposed to either placebo (n = 9) or the antioxidants vitamin C (1 g/day) and E (235 mg/day) (n = 11). Blood samples and muscle biopsies were taken under resting conditions in association with the first (untrained state) and last (trained state) SIT sessions. In the placebo group, the blood plasma level of the neurotoxic quinolinic acid was lower (~30%) and the neuroprotective kynurenic acid to quinolinic acid ratio was higher (~50%) in the trained than in the untrained state. Moreover, muscle biopsies showed a training-induced increase in kynurenine aminotransferase (KAT) III in the placebo group. All these training effects were absent in the vitamin-treated group. In conclusion, KP metabolism was shifted towards neuroprotection after three weeks of SIT in elderly men and this shift was blocked by antioxidant treatment.
|
|
| 2. |
- Agudelo, LZ, et al.
(författare)
-
Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2767-
-
Tidskriftsartikel (refereegranskat)abstract
- The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Schlittler, M, et al.
(författare)
-
Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans
- 2016
-
Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 310:10, s. C836-C840
-
Tidskriftsartikel (refereegranskat)abstract
- Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder.
|
|
| 6. |
- Wyckelsma, VL, et al.
(författare)
-
Vitamin C and E Treatment Blunts Sprint Interval Training-Induced Changes in Inflammatory Mediator-, Calcium-, and Mitochondria-Related Signaling in Recreationally Active Elderly Humans
- 2020
-
Ingår i: Antioxidants (Basel, Switzerland). - : MDPI AG. - 2076-3921. ; 9:9
-
Tidskriftsartikel (refereegranskat)abstract
- Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca2+ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.
|
|
| 7. |
- Dargeviciute, G, et al.
(författare)
-
Residual force depression following muscle shortening is exaggerated by prior eccentric drop jump exercise
- 2013
-
Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 115:8, s. 1191-1195
-
Tidskriftsartikel (refereegranskat)abstract
- We studied the relation between two common force modifications in skeletal muscle: the prolonged force depression induced by unaccustomed eccentric contractions, and the residual force depression (rFD) observed immediately after active shortening. We hypothesized that rFD originates from distortion within the sarcomeres and the extent of rFD: 1) correlates to the force and work performed during the shortening steps, which depend on sarcomeric integrity; and 2) is increased by sarcomeric disorganization induced by eccentric contractions. Nine healthy untrained men (mean age 26 yr) participated in the study. rFD was studied in electrically stimulated knee extensor muscles. rFD was defined as the reduction in isometric torque after active shortening compared with the torque in a purely isometric contraction. Eccentric contractions were performed as 50 repeated drop jumps with active deceleration to 90° knee angle, immediately followed by a maximal upward jump. rFD was assessed before and 5 min to 72 h after drop jumps. The series of drop jumps caused a prolonged force depression, which was about two times larger at 20-Hz than at 50-Hz stimulation. There was a significant correlation between increasing rFD and increasing mechanical work performed during active shortening both before and after drop jumps. In addition, a given rFD was obtained at a markedly lower mechanical work after drop jumps. In conclusion, the extent of rFD correlates to the mechanical work performed during active shortening. A series of eccentric contractions causes a prolonged reduction of isometric force. In addition, eccentric contractions exaggerate rFD, which further decreases muscle performance during dynamic contractions.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
