effects of immobilisation on skeletal muscle

Question 1

muscle protein balance

Answer 1

synthesis = degradation.

determined by nitrogen balance, stable isotope tracer determinations of protein turnover

Question 2

immobilisation

Answer 2

Muscle protein synthesis declines during immobilisation.
The mechanism for this is unclear, but appears to be unrelated to changes in the phosphorylation status of the Akt/mTOR pathway.

Muscle protein breakdown probably increases, but not to anywhere near the same extent as the decrease in muscle protein synthesis.

Question 3

muscle insulin resistance and immobilisation

Answer 3

The diminished ability of skeletal muscle to increase blood glucose disposal in response to elevated blood glucose and insulin concentrations

Question 4

muscle mass rehabilitation

Answer 4

Muscle protein synthesis increases dramatically with exercise. The mechanism for this increase in muscle mass during rehabilitation appears to be at least partly attributable to increased phosphorylation of the Akt/mTOR pathway.

Muscle protein breakdown appears to be inhibited by the instigation of rehabilitation exercise following immobilisation.

There is potential for nutritional and pharmacological intervention to facilitate muscle mass restoration following immobilisation induced atrophy by stimulating muscle protein synthesis (in the main).

Question 5

trauma and inflammation

Answer 5

Inflammation induces muscle wasting, which can be profound in severe cases (e.g. sepsis).

Muscle cytokines elevated

Muscle wasting is achieved by the marked inhibition of muscle protein synthesis AND increase in muscle protein breakdown.

Paralleled by molecular changes (unlike immobilisation per se)

Problem is heightened as muscle become very resistant to the anabolic effects of nutrients and hormones.

Inflammation induces muscle insulin resistance and impairs carbohydrate oxidation.

Question 6

major proteolytic systems in skeletal muscle

Answer 6

• lysosomal - cathepsin B, H, L and D
• Ca++ dependent - calpain 1,2,3
• ubiquitin-proteasome-dependent – ubiquitin E1, E2, E3 26S proteasome

Question 7

muscle protein breakdown in immobilisation

Answer 7

Administration of the proteasome inhibitor velcade

50% sparing of muscle weight following 3 days of cast immobilization in rodents

Little change in the total amount and phosphorylation state of signaling proteins thought to modulate muscle protein synthesis.

This led to the suggestion that muscle protein breakdown is the dominant mechanism by which muscle protein content is reduced by disuse in rodents, but not humans