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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– Unreachable training volume/intensity

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

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

mRNA concentrations reflect protein amount

mRNA concentrations reflect protein amount

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 upregulating the expression of proteins

involved in glycolysis, pH regulation, and angiogenesis

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

Time course of changes in mRNA and protein concentration

SERCA: sarco/endop1asmic reticu1um calcium.ATPase

Posttranslational modifications• Phosphorylation, subunit assembly, transport,

degradation• Protein synthesis rate < its incorporation into fiber as

functional component

Posttranslational modifications

• Ubiquitin proteasome system– Principal protein degradation mechanism in muscle

fibers

• ↑protein stability– ↑protein concentration without ↑mRNA

Adaptations can occur ex vivo

• adaptations to chronic electrical stimulation can be reproduced quite closely in denervated muscles and in culture– Do NOT require intact innervation– Do NOT require voluntarily contraction

Adaptations occur in specific sequence

Ex Biochem c8-signal transduction 15

Thresholds of activity for adaptation

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

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

Possible role of AMPK in adaptation in endurance training

Ex Biochem c8-signal transduction 20

Hormone nuclear receptors

Ex Biochem c8-signal transduction 21

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 22

Class II hormone nuclear receptor

Ex Biochem c25-act transcript 23

24

粒線體生合成的基因調控機制

Reznick et al, 2006

Ex Biochem c8-signal transduction 25

Proposed mechanism

PGC1a: peroxisome proliferator-activated receptor coactivator-1alpha

Ex Biochem c8-signal transduction 26

27Wang YX, PLOSB 2004

WT: wild type

TG: transgenic, expression of an activated form of PPARdelta in skeletal muscle

GW501516, GW1516PPARdelta agonist