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Chapter 6. muscular mechanism in aerobic endurance training

Chapter 6. muscular mechanism in aerobic endurance training. PF. Gardiner, Advanced neuromuscular exercise physiology. Limitations of techniques. Muscle biopsy Combination of fiber types Representative of entire muscle? Chronic electric stimulation Non-voluntary

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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

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