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J. Biol. Chem., Vol. 265, Issue 15, 8550-8557, 05, 1990
Role of different proteolytic systems in the degradation of muscle proteins during denervation atrophy
K Furuno, MN Goodman and AL Goldberg
Department of Cellular and Molecular Physiology, Harvard Medical School, Boston, Massachusetts 02115.
In order to clarify the cellular mechanisms of denervation atrophy of
skeletal muscle, we have studied protein turnover in denervated and control
rat soleus muscles in vitro under different conditions. By 24 h after
cutting the sciatic nerve, overall protein breakdown was greater in the
denervated soleus than in the contralateral control muscle, and by 3 days,
net proteolysis had increased about 3-fold. Since protein synthesis
increased slightly following denervation, the rise in proteolysis must be
responsible for the muscle atrophy and the differential loss of contractile
proteins. Like overall proteolysis, the breakdown of actin (as shown by
3-methyl-histidine production by the muscles) increased each day after
denervation and by 3 days was 2.5 times faster than in controls. Treatments
that block the lysosomal and Ca2(+)-dependent proteolytic systems did not
reduce the increase in overall protein degradation and actin breakdown in
the denervated muscles (maintained in complete medium at resting length).
However, the content of the lysosomal protease, cathepsin B, increased
about 2-fold by 3 days after denervation. Furthermore, conditions that
activate intralysosomal proteolysis (incubation without insulin or amino
acids) stimulated proteolysis 2-3-fold more in the denervated muscles than
in controls. Also, incubation conditions that activate the Ca2(+)-
dependent pathway (incubation with Ca2+ ionophores or allowing muscles to
shorten) were 2-3 times more effective in enhancing overall proteolysis in
the denervated muscle. None of these treatments affected 3-methylhistidine
production. Thus, multiple proteolytic systems increase in parallel in the
denervated muscle, but a nonlysosomal process (independent of Ca2+) appears
mainly responsible for the rapid loss of cell proteins, especially of
myofibrillar components.

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Copyright © 1990 by the American Society for Biochemistry and Molecular Biology.
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