molecular responses to resistance exercise Flashcards
muscle breakdown and synthesis
if synthesis>breakdown then muscle hypertrophy will occur (if paired with resistance exercise)
if muscle synthesis<breakdown then muscle atrophy will occur (if muscle is not being used)
if synthesis and breakdown are in equilibrium then the muscles will stay the same size
hypertrophy
r
resistance exercise training= hypertrophy of skeletal muscle fibres
making new muscle proteins requires the coordinated processes of transcription and translation
cellular and molecular regulation of hypertrophy
muscle fibre- muscle cells- are multinucleated
proteosomes- responsible for breaking down muscle proteins
satellite cell- lie on periphery of muscle fibre
resistance exercise and protein synthesis
resistance exercise increases protein synthesis
the effect is somewhat load dependent
protein translation
has 4 key regulatory steps
- activation
- initiation
- elongation
- termination
initiation- if you can speed up translation intitation you will be able to get a lot more proteins synthesis- is a key phase in the regulaiton of PS
molecular regulation of PS (mTOR)
control of protein translation
- mTOR and its associated signalling proteins = protein kinases
- protein kinases chemically add phosphate groups to downstream proteins and in turn increase/decrease their acitvity
- one protein phosphorylates one and then there is a domino effect
- activation of mTOR signalling ultimately results in an increase in translation initiation
studies- mTOR
in rats
- positive correlation observed between p70s6 kinase activation 6hrs after stimulation and total muscle mass after 6 weeks of training
in humans
- looking at leg extension either performing slow or fast contractions
-slow contraction increased p70s6k
synergistic ablation
is hard to do in humans so mostly done in rats
- can remove the gastrocnemius and soleus so when rats are walking, plantaris will take the load
- muscle will grow to about double the size in a couple of weeks
- shows compensatory hypertrophy
rapomycin
will directly bind and inhibit mTOR
p706sk activity was highest in the compensatory hypertrophy group and lower in the CH and rap group
rapamycin completely prevents muscle growth in response to CH so shows that mTOR is a very important regulator of muscle growth
resistance exercise and PS
resistance exercise increases muscle protein synthesis
over time, this transient increase in MPS results in muscle growth (positive protein balance)
increased MPS is dependent on mTOR signalling
mRNA
where does mRNA come from
for an increase in the number of myofibrillar proteins (hypertrophy) there are 2 possibilities
1. RE increases transcription of myofibrillar mRNA
2. ribosomes just translate the avaible mRNA faster
very large transcriptional response to exercise- mroe genes being transcribed
- changes in mRNA levels do not change in myosin and actin pre and post exercise
- no change in myofibrillar mrna levels (must be due to ribosomes)
i
ribosomal efficiency
study showing rna activity in control and exercise groups
increase in protein synthesis is due to increase in ribosomal activity allowing us to get more RNA
resistance exercise and transcription
RE induces very large alterations in gene expression within skeletal muscle
no evidence that myofibrillar gene expression changes with RE
the icnrease in protein synthesis is due to an increase in ribosome efficiency
ribosomal biogenesis + rRNA
as muscle undergoes hypertrophy, there is an increase in RNA content
rRNA accounts for approx 80% of total RNA
rRNA is the principal component of ribosomes
across all rRNAs, there is an increase over the chronic exercise period
shows that there is an increase in number of ribosomes in muscle
study- rRNA abundance
4 weeks resistance training
non response, moderate and extreme response
rRNa abundance unchanged between non and moderate responders
extreme have a large increase in rRNA abundance
suggests that increase in rRNA is associated with an increase in muscle growth
ribosomal biogenesis and hypertrophy- CX5461
CX5461 - inhibits ribosome biogenesis - can be used to see if this RB is important for muscle growth (cells growing on petri dish)
results showed lower myotube diameter in cells that were stimulated to grow but had CX5461- showing that CX does actually inhibit muscle growth showing RB is crucial for muscle growth
resistance exercise and ribosome biogenesis
no increase in markers of ribosome biogenesis after acute RE
RE is associated with increased ribosome biogenesis
ribosome biogenesis correlates with muscle size following trainng
absolute requirement for ribosome biogenesis for muscle hypertrophy is not fully understood
ribosome biiogenesis is controlled in part by mTOR
satellite cells and resistance training
myonuclei are responsible for transcription and ribosome biogenesis; therefore as muscle grows, do we need more myonuclei?
satellite cells are muscle stem cells located on the periphery of muscle fibres
stem cells- ability to self renew–> some stem cells will differentiate and some will become stem cells again
they account for 2-5% of total nuclei in muslce
myotrauma- exercise
satellite cells - myotrauma
before myotrauma- satelite cells are very dormant
after- they become activated
-starts to proliferate
-some will self renew
- some will fuse with damaged myofibres, to try and assist in the repair of damage
- once it is fused, the myofiber has an extra nuclei and this can happen 100s of times
- more nuclei- more likely to transcribe and transcript
myonuclear domain
area of sarcoplasm controlled by a nucleus
calculated as fibre number/number of nuclei
2 scenarios proposed
1- fibres grow without myonuclear addition (no new myonuclear coming in) - MND expands
X section of the fibre has got bigger so myonuclear domain has increases (starts and ends with 4 cells but fibre is bigger)
2- fibres grow but require myonclear addiition= MND remains constant
- needed more myonuclear so now have 6 myonuclei
- each section of cell has got the same area as the original cells
(starts with 4 cells and expands to 6)
(look at pics in notes)
study- fibre area and detraining
90 days training and detraining
number of myonuclei doesnt change- meaning muscle can grow without satellite cells needed to increase the number of myonuclei - so that they can make ribosomes which allows muscle to grow
satellite cells are thought to be primary source for myonuclei - are activated, proliferate and fuse with muscle fibres which increases myonuclear number
satellite cells required for hypertrophy- tamoxifen
study
- can genetically modify animals so that when they take tamoxifen, it will kill satellite cells
from muscle weight can see that it is not a sig diff so show satellite cells are not needed for muscle growth
evidence says that you do not need satellite cells for muslces to get bigger
role of proteolysis
in resistance exercise adaptation
ubiquitin- proteosome pathway
proteosome- waste bin of the cell, breaks up protein into its monomers
can be used again to build new proteins
occurs in all cells
muscle cells- have specific E3 ubiquitin ligases (attach ubiquitin to target protein)
hypertrophic stimuli- increases E3 ubiquitin ligases
activity of enzymes in proteosome increases- more amino acids which can be used by for protein synthesis
inhibition of proteolysis
impairs muscle size and growth
- mice that dont have functional proteosome so cant break down protein
- mice that dont have muscle protoesome have have smaller muscle weight and weaker
- RPT3- subunit of 26S proteosome and essential for protein degradation (used in studies)
proteolysis and hypertrophy
protoelysis- breakdown and recycling of proteins that are damaged, misfolded or no longer needed
- - Reisistance exercise stimulates proteolysis
- Mediated largely through ubiquitin-proteasome system
- Inhibition of proteolysis impairs muscle function
- Increased proteolysis is less than increase in MPS (net balance is positive)
- Feeding (insulin and AAs) suppress proteolysis – therefore net balance is even more positive
summary
- RT induced skeletal muscle hypertrophy is stimulated by MPS on ribosomes
- mTOR is important (required?) for load induced hypertrophy
- Ribosomal efficiency drives increased MPS in short term
- Increase ribosomal capacity is associated with hypertrophy in the long term
- Satellite cells are required to maintain transcription and ribosomal biogenesis when
hypertrophy exceeds a ceiling size - RE is associated with increased proteolysis in skeletal muscle. This helps with the remodelling of skeletal muscle
p706S
a protein kinase involved in the transisiton initiation phase of mTOR signalling pathway
phosphorylates ribosomal proteins
promotes muscle protein synthesis
