Activation of Akt as a potential mediator of adaptations that reduce muscle injury.

UNLABELLED: Contraction-induced injury occurs when a muscle is stretched while activated (lengthening contraction). Exposure to a bout of lengthening contractions results in protection from subsequent lengthening contraction-induced injury as well as an elevation in phosphorylated Akt and p70S6K. Whether Akt or p70S6K is involved in the protection from contraction-induced injury is unclear. To test for a specific role of Akt and/or p70S6K to induce protective adaptations, we used a conditioning protocol of passive stretches that reduces contraction-induced injury with minimal involvement of other cellular responses that have been associated with the Akt signaling pathway, such as increased metabolism, cell growth, and cell death.

PURPOSE: To determine whether activation of Akt or p70S6K is necessary to induce protective adaptations.

METHODS

Extensor digitorum longus muscles of anesthetized mice were administered 75 lengthening contractions in situ with or without previous exposure to 75 passive stretches 1 h, 24 h, 3 d, or 14 d prior to lengthening contractions.

RESULTS

Compared with unconditioned muscles, the deficit in isometric force and number of injured fibers 3 d following lengthening contractions were smaller by half for passive-stretch-conditioned muscles from all time points. Phosphorylation of Akt and p70S6K were analyzed by Western blot 0 or 3 h following either lengthening contractions or passive stretches. Whereas lengthening contractions increased phosphorylation of Akt at 0 h and p70S6K at 3 h, passive stretches did not at any time increase phosphorylation of Akt or p70S6K despite reducing contraction-induced injury.

CONCLUSION

Activation of neither Akt nor p70S6K is necessary to induce adaptations that reduce the severity of contraction-induced injury.