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

6

Transcription Factors

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

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

Ex Nutr c8-protein 14

mTOR (mammalian target of rapamycin) 訊息傳遞路徑：上游

Laplante & Sabatini, 2012

Ex Nutr c8-protein 15

mTOR 訊息傳遞路徑：下游

Laplante & Sabatini, 2012

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

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

Ex Biochem c8-protein synthesis 26

Role of connective tissue

• ↑collagen synthesis in tendons• ↑muscle collagen synthesis• ↑ Iysyl oxidase), an enzyme involved in cross-linking

collagen

Ex Nutr c8-protein 28

重量訓練後補充蛋白質時機與效果

Kerksick, 2012

Ex Nutr c8-protein 29

各種蛋白質來源對肌肉合成的效果結合長期重量訓練

Kerksick, 2012