satellite cell
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SATELLITE CELL ADDITION IS/IS NOT OBLIGATORY FOR SKELETAL MUSCLE HYPERTROPHY
Nuclear Domain:• Constant ratio• Myonuclei/cell volume
HYPERTROPHYAt myofiber: Cross-sectional area Mass Protein content Cytoplasm volume Myonuclei #
Satellite cells: • Progenitor cells
• Similar to stem cells• Muscle precursor cells
• Location:• Basal lamina • Myofiber membrane
• Function:• Muscle growth• Muscle regeneration
During postnatal growth:Satellite cell role • Myonuclear addition• Myofiber formation
Synergist ablation› surgical removal of
synergistic muscle Testosterone Clenbuterol
› β- Adrenergic agonist Stretch Overload Exercise
Satellite CellACTIVATION
+PROLIFERATION
Type I and Type IIMyofiber(s)
TRANSCRIPTION TRANSLATION
Inhibition of myonuclear addition prevents hypertrophy
Satellite cell ablation by local gamma irradiation Assessing hypertrophy
› Muscle mass or myofiber cross-sectional area is measured
Assessing satellite cell activity› Enumeration, bromodeoxyuridine labeling, myoD
expression, and increases in myonuclear number
Lesions on satellite cells Affects non-muscle cells that may prevent factors
that regulate satellite cell activity Totally prevented local hypertrophy in adult rodents
after synergist ablation Does not effect adaptive changes in myosin heavy
chain expression Also, gamma irradiation used in the studies cited
does not meet levels commensurate with damage and necrosis
Important: Multiple time points are necessary to determine the roll of satellite cells!› Many studies did not use later time points
“Myonuclear domain ceiling”› Small increments may not change satellite cell #› But additional increases may elicit satellite cell
proliferation
Satellite cell addition is NOT obligatory for skeletal muscle hypertrophy (O’Connor & Pavlath)
“Obligatory” =› Mandatory, necessary, or essential
Provide evidence of skeletal muscle hypertrophy in the absence of satellite cell addition
Investigated the effect of 1. Administered pharmacological agent 2. Contraction induced 3. Gamma irradiation
Induced skeletal muscle hypertrophy in the absence of any increase in DNA content
OR increases in myonuclear number
Cimaterol/ clenbuterol Administered via oral and intravenous
› Stimulates lipolysis› Stimulates protein synthesis› Stimulates blood flow› Increases acute mobilization of nitrogen› Increases amino acid uptake in the muscles
Conclusions Examined:
› Whole body weight› Muscle weight› Fiber diameter› Myonuclei number
Induced skeletal muscle hypertrophy without any increase in satellite cells or increase in myonuclear number
Increase in protein synthesis (RNA increase)
Sedentary Control No Reps
Mod Freq/Mod Resistance
24 Reps, 500 gms
High Freq/ Low Resistance
192 Reps, 0 gms
High Freq/ High Resistance
192 Reps, 800-1100 gms
Wong & Booth, 1990
Results:› Mod/Mod- No difference after acute exercise bouts› High Freq/Low Resistance - Protein synthesis
increased 38%› High Freq/High Resistance- No further increase in
protein synthesis over low resistance groupWong & Booth, 1990
Exercise Protein Synthesis
DNA Content Muscle Hypertrophy
Concentric Increase Increase None
Eccentric Increase No Increase Increase
Results:
Electrical stimulation alone did not cause muscle hypertrophy
Combined with static stretch, protein synthesis increased.
Increase rates of ribosomal capacities Increase in RNA No change in total DNA per muscle
Goldspink et al., 1995
Satellite cell addition does not occur as measured by DNA content or nuclear number
Inhibition of satellite cell proliferation does not inhibit skeletal muscle growth
Increase in hypertrophy due to increase in protein synthesis
The following conditions need to be addressed:› Analysis of time points (early and late) after
application of a hypertrophic stimulus› Sufficiently large increases in myofiber cross-sectional
area or diameter › Identify myonuclear number using a method to
clearly depict the sarcolemma› To show cause and effect rather than correlation after
satellite cell removal
Various models of hypertrophy fail to satisfy one or more of these criteria › Do not provide conclusive evidence against the
necessity for satellite cells in hypertrophy
Satellite cell addition is obligatory, but set in later stages due to a “myonuclear domain ceiling”
Satellite cell and muscle regeneration well documented Satellite cell role with hypertrophy debated Timing of myonuclei addition unknown Multiple time points required to determine satellite cell
role in hypertrophic model Acute response:
› Enhanced transcription by myonuclei Hypertrophic response may depend on the stimulus
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