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Chapter 6. muscular mechanism in aerobic endurance training
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Chapter 6. muscular mechanism in aerobic endurance training

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  1. Chapter 6. muscular mechanism in aerobic endurance training PF. Gardiner, Advanced neuromuscular exercise physiology

  2. Limitations of techniques • Muscle biopsy • Combination of fiber types • Representative of entire muscle? • Chronic electric stimulation • Non-voluntary • Unreachable training volume/intensity

  3. Coordination of muscle protein systems • The coordinated expression of many proteins simultaneously • common transcription factors and metabolic signals that promote the expression of several genes • Changes in type 1 fibers,including heavy chains, light chains, and thin filament proteins

  4. Pre-translational control • Changes in mRNA abundance • Transcription rate, mRNA processing, mRNA stability • Can happen after several contractions, up to several hours after exercise • In chronically stimulated muscles, mRNA levels generally reflect protein levels • Mitochondrial mRNA/DNA ratio remain unchanged • Mitochondria proliferation ↑DNA

  5. mRNA concentrations reflect protein amount

  6. mRNA concentrations reflect protein amount

  7. Hypoxic training • Hypoxia alone has a unique stimulatory effect • expression of several genes associated with improved metabolism and performance. • Induction of hypoxia-inducible factor-1 (HIF-1) • involved in upregulatingthe expression of proteins involved in glycolysis, pH regulation, and angiogenesis

  8. Translational control • Initiation, elongation, termination • Receptor-binding and mitogen-activated protein kinase (MAPK) signaling systems • ↑ribosomal RNA 7X in first 2 weeks of stimulation in rabbit muscles • Enhanced translational efficiency • Translation may be altered in order to coordinate the expression of two proteins whose functions are closely linked

  9. Time course of changes in mRNA and protein concentration SERCA: sarco/endop1asmic reticu1um calcium.ATPase

  10. Posttranslational modifications • Phosphorylation, subunit assembly, transport, degradation • Protein synthesis rate < its incorporation into fiber as functional component

  11. Posttranslational modifications • Ubiquitin proteasome system • Principal protein degradation mechanism in muscle fibers • ↑protein stability • ↑protein concentration without ↑mRNA

  12. Adaptations can occur ex vivo • adaptations to chronic electrical stimulation can be reproduced quite closely in denervatedmuscles and in culture • Do NOT require intact innervation • Do NOT require voluntarily contraction

  13. Adaptations occur in specific sequence

  14. Ex Biochem c8-signal transduction

  15. Thresholds of activity for adaptation

  16. Metabolic signals and adaptation • Metabolic signaling • ATP/ADP • AMP-activated kinase (AMPK) • PPARs: free fatty acids • Ca2+ signaling • ↑intracellular Ca after days of electric stimulation • Calcineurin; calcium-regulated phosphatase • Ionophore A23187

  17. Metabolic signals and adaptation • Mechanical signaling • Activation of MAPK signaling pathways, activated by several types of stresses • JNK family: stress-activated protein kinases • Hormones, autocrine or paracrine factors • Insulin-like growth factor 1 (IGF-1) • Hypoxia, H+, reactive-oxygen species

  18. Possible role of AMPK in adaptation in endurance training

  19. Hormone nuclear receptors Ex Biochem c8-signal transduction

  20. 25.7 Response Elements Are Recognized by Activators • Response elements may be located in promoters or enhancers. Figure 25.11 Ex Biochem c8-signal transduction

  21. Class II hormone nuclear receptor Ex Biochem c8-signal transduction

  22. Ex Biochem c25-act transcript

  23. 粒線體生合成的基因調控機制 Reznick et al, 2006

  24. Proposed mechanism Ex Biochem c8-signal transduction PGC1a: peroxisome proliferator-activated receptor coactivator-1alpha

  25. Ex Biochem c8-signal transduction

  26. WT: wild type TG: transgenic, expression of an activated form of PPARdelta in skeletal muscle GW501516, GW1516PPARdelta agonist Wang YX, PLOSB 2004