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Chapter 8. Muscle molecular mechanism in strength training

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  1. Chapter 8. Muscle molecular mechanism in strength training PF. Gardiner, Advanced neuromuscular exercise physiology

  2. Overview • Mitogenic: growth-promoting • Stress and strain on muscular structures as signals through mechanotransduction receptors via several pathways • Acute resistance exercise ↑protein synthesis and degradation • Effect may last for hours to days • Relatively short exposure is sufficient in animal studies

  3. Acute resistance exercise increase both protein synthesis and breakdown

  4. Stretch as a Signal for Adaptation • Force as a signal to resistance-related adaptations • ↑muscle weight when rabbit muscles are immobilized in a lengthened position • result of increased muscle fiber length • electrical stimulation added effect • stretch, independent of increased contractile activity, can stimulate protein synthesis via several pathways

  5. Mitogen-activated protein kinases, MAPK • Central factor for stretch-related signal transduction • Induced by G-protein pathway • Downstream • FOS, JUN • MAPK-regulated transcription factors • stretch causes physical deformation of the 3D configuration of the transmembrane receptors • Activation of that receptor, similar to attachment of its ligand • integrin

  6. Transcription Factors

  7. 25.7 Response Elements Are Recognized by Activators • Response elements may be located in promoters or enhancers. Figure 25.11 Ex Biochem c25-act transcript

  8. Stretch-related signal transduction

  9. Detailed MAPK pathways http://en.wikipedia.org/wiki/File:MAPKpathway.jpg

  10. Ex Biochem c25-act transcript

  11. Insulin-like growth factor -1, IGF-1 • Produced by liver and muscle • Stimulate cell hypertrophy in cultured myotubes • ↑ initiating factors in translation: eIF4E- eIF4G (eukaryotic initiating factor) • IGF-1 mRNA and protein ↑after resistance exercise

  12. Akt and mTOR Cascade • Akt (protein kinase B, PKB) activated by IGF-1 • mTOR(Mammalian target of rapamycin): activated by Akt • Also activated by leucine • Downstream targets of mTOR: proteins that control translation • S6K1 (p70S6K), eIF4G, and eIF4E binding protein 4EBPl • After exercise: ↑, then↓ • a transient increase in translation initiation • when repeated after each training session, results in muscle hypertrophy

  13. Role of mTOR in response to resistance training

  14. mTOR (mammalian target of rapamycin) 訊息傳遞路徑:上游 Ex Nutr c8-protein Laplante & Sabatini, 2012

  15. mTOR 訊息傳遞路徑:下游 Ex Nutr c8-protein Laplante & Sabatini, 2012

  16. Proto-Oncogenes FOS, JUN, and MYC • Rapid ↑after mechanical stimulus • Bind to DNA • Important in muscles • FOS, JUN: bind to promoter region of several growth-related genes • MYC: involved in mitosis 有絲分裂

  17. JUN, FOS, MYC pathways

  18. Passive stretch of rabbit muscles

  19. Passive stretch and electrical stimulation of rabbit muscles

  20. Other factors • Muscle Regulatory Factor (MRF) Genes • active during muscle development, but present at negligible levels in normal adult muscles • Myf-5, MyoD1. MRF4. and myogenin • ↑after mechanical stimulus • Myostatin • negative influence on muscle growth • ↓ after mechanical stimulus

  21. Posttranslational changes • ↑RNA activity: units of protein synthesis per unit time per unit RNA after acute stimulus • ↑ribosome • ↑ribosomal protein, ↑total RNA (mostly ribosomal RNA) • ↑ numerous eukaryotic initiation factors (eIF) that facilitate peptide initiation at the ribosome • mRNAs). Downregulated • Downregulate (↓) genes in catabolic effects • elongation factor-2 kinase (which inactivates elongation factor 2) • cathepsin C (a lysosomal protease)

  22. Intracellular Proteolytic Systems • calcium-activatcdncutralproteases (calpains) • The Iysosomalproteases • ATP-ubiquitin-dependent pathway • May be ↓ by ß-hydroxy-ß-melhylbutyrate (HMB) • All ↑after acute resistance exercise • Apoptosis (細胞凋亡, programmed cell death) ↑after acute resistance exercise

  23. Ubiquitin pathway

  24. 8.2 Protein Synthesis: Initiation, Elongation, and Termination • The ribosome has three tRNA-binding sites. • An aminoacyl-tRNA enters the A site. • Peptidyl-tRNA is bound in the P site. • DeacylatedtRNA exits via the E site • Translocation: ribosome move one triplet along mRNA Ex Biochem c8-protein synthesis Figure 8.3

  25. Figure 8.23: 43S complex binds to mRNA-factor complex. PABP: poly(A)-binding protein Ex Biochem c8-protein synthesis

  26. Ex Biochem c8-protein synthesis

  27. Role of connective tissue • ↑collagen synthesis in tendons • ↑muscle collagen synthesis • ↑ Iysyl oxidase), an enzyme involved in cross-linking collagen

  28. 重量訓練後補充蛋白質時機與效果 Ex Nutr c8-protein Kerksick, 2012

  29. 各種蛋白質來源對肌肉合成的效果結合長期重量訓練各種蛋白質來源對肌肉合成的效果結合長期重量訓練 Ex Nutr c8-protein Kerksick, 2012