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Article |

Sepsis Increases Oxidatively Damaged Proteins in Skeletal Muscle

Julie M. Fagan, PhD; Mita Ganguly, PhD; Greg Tiao, MD; Josef E. Fischer, MD; Per-Olof Hasselgren, MD
Arch Surg. 1996;131(12):1326-1332. doi:10.1001/archsurg.1996.01430240080011.
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Background:  Muscle wasting and negative nitrogen balance are common findings in septic patients. It is not clear what signals this loss of body protein. Proteins modified by reactive oxygen species have been shown to be rapidly degraded.

Objective:  To test the hypothesis that sepsis results in an increased amount of oxidatively damaged proteins in skeletal muscle.

Methods:  Exposure of proteins to reactive oxygen species results in the incorporation of carbonyl groups into amino acids with metal binding sites. The formation of carbonyl group derivatives in sarcoplasmic and myofibrillar proteins was measured in the extensor digitorum longus and soleus muscles of septic rats 4 to 48 hours after cecal ligation and puncture and in control rats that underwent sham operation.

Results:  Protein carbonyl content was increased 8 and 16 hours after cecal ligation and puncture in the extensor digitorum longus and soleus muscles, respectively. When muscles were incubated in vitro, the carbonyl content in protein decreased in muscles from septic rats but not in muscles from rats that had the sham operation. The loss of carbonyl groups in incubated septic muscles occurred also in energy-depleted muscles.

Conclusions:  Muscle proteins are oxidatively damaged during sepsis and an energy-independent proteolytic pathway participates in the degradation of these proteins. Damage to muscle proteins by reactive oxygen species may signal the selective removal of postsynthetically modified proteins, contributing to accelerated muscle protein degradation in sepsis.Arch Surg. 1996;131:1326-1332


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