Increased Heat Shock Protein Expression Decreases Inflammation in Skeletal Muscle During and after Frostbite Injury

Curr Mol Med. 2020;20(9):733-740. doi: 10.2174/1566524020666200407083131.

Abstract

Background: Frostbite injury results in serious skeletal muscle damage. The inflammatory response due to frostbite causes local muscle degeneration. Previous studies have shown that heat shock proteins (hsps) can protect against inflammation. In addition, our previous studies showed that increased expression of hsp70 is able to protect skeletal muscle against cryolesion.

Methods: Therefore, our aim was to determine if the induction of the heat shock proteins are able to minimize inflammation and protect skeletal muscle against frostbite injury.

Results: In the present study, we used the hsp90 inhibitor, 17-dimethylaminoethylamino- 17-demethoxygeldanamycin (17-DMAG), which was administered within 30 minutes following frostbite injury. Rat hind-limb muscles injected with 17-DMAG following frostbite injury exhibited less inflammatory cell infiltration as compared to control rat hind-limb muscles. In agreement with this observation, it has been observed that increased hsp expression resulted in decreased inflammatory cytokine expression. Additionally, we found that the administration of 17-DMAG after frostbite injury can preserve muscle tissue structure as well as function.

Conclusion: It has been concluded that compounds such as 17-DMAG that induce the heat shock proteins are able to preserve skeletal muscle function and structure if injected within 30 minutes after frostbite injury. Our studies provide the basis for the development of a potential therapeutic strategy to treat the injury caused by frostbite.

Keywords: 17-DMAG; Frostbite injury; heat shock proteins; hsp90 inhibitor; inflammation; skeletal muscle.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Benzoquinones / pharmacology*
  • Cytokines / metabolism
  • Frostbite / complications*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lactams, Macrocyclic / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Benzoquinones
  • Cytokines
  • Heat-Shock Proteins
  • Lactams, Macrocyclic
  • Protective Agents
  • 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin