W10 - molecular responses to resistance exericse Flashcards

1
Q

What is meant by atrophy?

What is the main contributor to muscle hypertrophy?
How is it made?

A

Atrophy - catabolism, muscle breakdown. Ageing or disease causes this

Resistance training is the main contributor to muscle hypertrophy
- Over the course of a week Synthesis and breakdown are relatively equal
- Making new muscle proteins requires the coordinated process of
1. Transcription
2. Translation

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2
Q

What are the elements of cell and molecular regulation of load induced hypertrophy?

A
  1. Protein synthesis and it’s regulation
  2. Transcription
  3. Ribosome biogenesis
  4. Satellite cell mediated myonuclear addition
  5. Proteolysis (protein breakdown)
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3
Q

Why is muscle protein synthesis different before and after exercise?

What can induce this further when training?

A

FSR (muscle protein synthesis) - before/after exercise, at different ages
- Measured through stable isotope measurement techniques
- Protein in muscle is being made faster after a bout of exercise, more when exercise is pushed more
- Muscle protein synthesis, is the rate of translation of protein within the muscle

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4
Q

What are the 4 regulatory steps of translation?

A
  • activation
  • initiation
  • elongation
  • termination
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5
Q

How is protein translation controlled/regulated?

A
  • mTOR(mechanistic target of meromyosin) and its associated signalling proteins are termed protein kinases
    • Protein kinases(add a Phosphate group to another protein) chemically add phosphate groups to ‘downstream’ proteins and in turn increase/decrease their activity.
    • The activation of mTOR signalling ultimately results in an increase in translation initiation
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6
Q

What protein is highly associated with the amount of muscle growth?

A
  • The extent that mTOR was switched on during exercise, is proportional to the amount of muscle growth that occurs afterwards
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7
Q

Name an mTOR inhibitor:
how does it affect muscle growth?

A
  • Rap - rapomyosin, an inhibitor of mTOR
    • Rap stops muscle from growing, by inhibiting mTOR pathways. So mTOR drives muscle hypertrophy
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8
Q

What is synergistic ablation?

A
  • Synergistic ablation(cut out) - all of the load then goes through one muscle, causing the muscle to grow rapidly, doubling in size (compensatory hypertrophy)
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9
Q

What can be used to view MPS in a lab?

A
  • We can measure muscle protein synthesis
    Any new muscle made will incorporate stable isotope tracers, to see how much new muscle has been made
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10
Q

What increases mRNA content?

A
  • RE increases transcription of myofibrillar mRNA
    • Ribosomes just translate the available mRNA faster
  • Myofibrillar proteins make up 80% of muscle
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11
Q

What is meant by ribosomal efficiency?

A
  • Ribosomal efficiency - when the protein is being translated more and faster, increased capacity
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12
Q

How does resistance exercise impact the rate of transcription?

A
  • RE induces very large alterations in gene expression within skeletal muscle
  • No evidence that myofibrillar gene expression changes with RE(resistance exercise)
  • The increase in protein synthesis is due to an increase in ribosome efficiency
    • Increases its capacity to grow by increase rRNA, as ribosomes help with protein synthesis for growth
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13
Q

name a ribosome biogenesis inhibitor:

A

CX-5421 - a ribosome biogenesis inhibitor

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14
Q

How does resistance exercise impact ribosome biogenesis?

A
  • No increase in markers of ribosome biogenesis after acute RE.
  • RT is associated with increased ribosome biogenesis.
  • Ribosome biogenesis correlates with muscle size following training.
  • The absolute requirement for ribosome biogenesis for muscle hypertrophy is not fully understood.
  • Ribosome biogenesis is controlled (partly) by mTOR
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15
Q

What are satellite cells?

A

Satellite cells are muscle stem cells( none specific cell, that can become any type of cell in your body) that are located on the periphery of muscle fibres
They account for 2-5% of total nuclei in muscle.
- Myonuclei (nuclei in a muscle cell)

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16
Q

What affect does exercise have on satellite cells?

A
  1. myotrauma = satellite activation and proliferation
    Satellite cells proliferate extensively, increasing numbers in damaged area of the muscle when activated
  2. chemotaxis to injured fibre
  3. fusion to damaged myofiber(hypertrophy), producing new myofibers
    - The fusion of muscle fibres only occurs in muscle fibres that are there in humans (rodents produce new muscle fibres, hyperplasia)
    - The fusion contributes a new nucleus(Myonuclei) to the muscle fibre - Myonuclei addition
  4. regenerated myofiber with central nuclei
  5. resting/quiescent satellite cell
17
Q

What is a MND?

How does hypertrophy effect this?

A

myonuclear domain - area of sarcoplasm controlled by a nucleus

  1. fibres grow without myonuclear addition = MND expands
  2. fibres grow but require myonuclear addition = MND remains constant
18
Q

Describe the ubiquitin proteasome pathway:

A

Ubiquitin proteasome pathway - main pathway for muscle protein breakdown
- Multi-subunit complex that is responsible for muscle protein breakdown
- Cell targets the degradation of the proteasome (adding ubiquitin) as a flag. When enough is added(x5), the cell knows that the protein is ready for degradation
- Ubiquitinated protein gets shuttled to the proteasome where it gets broken-down

19
Q

What are the 2 important enzymes in the molecular regulation of muscle proteolysis?

A

MuRF1 and MAFbx

20
Q

What is the relationship between proteolysis and hypertrophy?

A
  • Resistance exercise stimulates proteolysis
  • Mediated largely through the ubiquitin-proteasome system
  • Inhibition of proteolysis impairs muscle function
    • You need to get rid of the old/damaged proteins. Remodelling is important.
      IMPORTANT NOTES
  • ↑ proteolysis is less than ↑ in MPS (net balance is positive)
  • Feeding (insulin and AAs) suppress proteolysis (therefore net balance even more positive) - causes more of a positive protein balance, causing muscle growth