Transcript Chapter 8. Muscle molecular mechanism in strength training

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
Acute resistance exercise increase both
protein synthesis and breakdown
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
Transcription Factors
6
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
7
Stretch-related signal transduction
Detailed MAPK pathways
http://en.wikipedia.org/wiki/File:MAPKpathway.jpg
Ex Biochem c25-act transcript
10
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
Role of mTOR in response to
resistance training
mTOR (mammalian target of rapamycin)
訊息傳遞路徑：上游
Ex Nutr c8-protein
Laplante & Sabatini,142012
mTOR 訊息傳遞路徑：下游
Ex Nutr c8-protein
Laplante & Sabatini,152012
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
JUN, FOS, MYC pathways
Passive stretch of rabbit muscles
Passive stretch and electrical
stimulation of rabbit muscles
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
Ubiquitin pathway
8.2 Protein Synthesis: Initiation,
Elongation, and Termination
• The ribosome has three tRNAbinding 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
Ex Biochem c8-protein synthesis
Figure 8.3
24
Figure 8.23: 43S complex
binds tosynthesis
mRNA-factor complex.
Ex Biochem c8-protein
PABP: poly(A)-binding protein
25
Ex Biochem c8-protein synthesis
26
Role of connective tissue
• ↑collagen synthesis in tendons
• ↑muscle collagen synthesis
• ↑ Iysyl oxidase), an enzyme involved in crosslinking collagen
重量訓練後補充蛋白質
時機與效果
Ex Nutr c8-protein
28
Kerksick, 2012
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
29
Kerksick, 2012