Sepsis increases oxidatively damaged proteins in skeletal muscle
J. M. Fagan, M. Ganguly, G. Tiao, J. E. Fischer and P. O. Hasselgren
Department of Animal Sciences, Rutgers University, New Brunswick, NJ, USA.
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.
