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Chapter 8. Muscle molecular mechanism in strength training. PF. Gardiner, Advanced neuromuscular exercise physiology. Overview. Mitogenic : growth-promoting Stress and strain on muscular structures as signals through mechanotransduction receptors via several pathways - PowerPoint PPT Presentation
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Chapter 8. Muscle molecular mechanism in strength training
PF. Gardiner, Advanced neuromuscular exercise physiology
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
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
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
Ex Biochem c25-act transcript 7
25.7 Response Elements Are Recognized by Activators
• Response elements may be located in promoters or enhancers.
Figure 25.11
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
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
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
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
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)
Intracellular Proteolytic Systems
• calcium-activatcd ncutral proteases (calpains)• The Iysosomal proteases• 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
Ex Biochem c8-protein synthesis 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.
• Deacylated tRNA exits via the E site
• Translocation: ribosome move one triplet along mRNA
Figure 8.3
Ex Biochem c8-protein synthesis 25Figure 8.23: 43S complex binds to mRNA-factor complex.PABP: poly(A)-binding protein
Role of connective tissue
• ↑collagen synthesis in tendons• ↑muscle collagen synthesis• ↑ Iysyl oxidase), an enzyme involved in cross-linking
collagen