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Activation of Akt as a Potential Mediator of Adaptations that Reduce Muscle Injury


Medicine & Science in Sports & Exercise: June 2006 - Volume 38 - Issue 6 - p 1058-1064
doi: 10.1249/01.mss.0000222832.43520.27
BASIC SCIENCES: Original Investigations

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.

1Institute of Gerontology and 2Departments of Molecular and Integrative Physiology and 3Mechanical Engineering, University of Michigan, Ann Arbor, MI; and 4Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, CO

Address for correspondence: Susan V. Brooks, Ph.D., Institute of Gerontology, The University of Michigan, 300 N. Ingalls, Ann Arbor, MI, 48109-2007; E-mail:

Submitted for publication July 2005.

Accepted for publication December 2005.

©2006The American College of Sports Medicine