17-(allylamino)-17-demethoxygeldanamycin drives Hsp70 expression but fails to improve morphological or functional recovery in injured skeletal muscle

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Abstract

SUMMARY

The stress inducible 70 kDa heat shock protein (Hsp70) is instrumental to efficient morphological and functional recovery following skeletal muscle injury because of its roles in protein quality control and molecular signalling. Therefore, in attempt to improve recovery, Hsp70 expression was increased with 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) prior to and following an intramuscular injection of barium chloride (BaCl2) into the tibialis anterior (TA) of healthy young mice. To assess recovery, regenerating fibre cross-sectional area (CSA) of the TA andin vivopeak isometric torque produced by the anterior crural muscles (TA, extensor digitorum longus and extensor hallucis muscles) were analyzed for up to 3 weeks after the injury. Because treatment of 17-AAG and Hsp70 are known to influence inflammatory and myogenic signalling, tumor necrosis factor-α(TNF-α) and myogenin content were also assessed. This study reports that 17-AAG was effective at up-regulating Hsp70 expression, increasing content fivefold in the uninjured muscle. However, this significant increase in Hsp70 content did not enhance morphological or functional recovery following the injury, as the return of regenerating fibre CSA andin vivopeak isometric torque did not differ compared to that of the injured muscle from the vehicle treated mice. Treatment with 17-AAG also altered TNF-αand myogenin content, increasing both to a greater extent after the injury. Together, these findings demonstrate that although 17-AAG may alter molecular makers of regeneration, it does not improve recovery following BaCl2-induced skeletal muscle injury in healthy young mice.

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