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Deficiency of the Bax gene attenuates denervation‐induced muscle wasting
Author(s) -
Siu Parco M,
Pistilli Emidio E,
Peterson Jonathan M,
Always Stephen E
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a390-c
Subject(s) - wasting , denervation , gene , microbiology and biotechnology , medicine , biology , genetics
Apoptosis has been implicated in mediating pathologic muscle wasting. The purpose of the present study was to determine the effect of interference of apoptosis on muscle wasting during denervation. We tested the hypothesis that denervation‐induced muscle wasting is ameliorated in skeletal muscle of CB57BL/6 mice that are deficient of the pro‐apoptotic Bax gene. After fourteen days of muscle denervation, muscle wasting was evident in both wild‐type and Bax ‐/‐ muscles but reduction of muscle weight was attenuated in Bax ‐/‐ mice. Apoptotic DNA fragmentation increased in wild‐type denervated muscle whereas the increase in Bax ‐/‐ mice did not reach significant level. Mitochondrial AIF and Smac/DIABLO releases and Bcl‐2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a similar extent in wild‐type and Bax ‐/‐ muscles following denervation. Mitochondrial cytochrome c release was elevated in wild‐type denervated muscle but the increase was suppressed in Bax ‐/‐ mice. Increases in caspase‐3 and ‐9 activities and oxidative stress markers H2O2, MDA/4‐HAE and nitrotyrosine were all evident in denervated wild‐type muscle but these changes were absent in Bax ‐/‐ muscle. Moreover, ARC increased exclusively in denervated Bax ‐/‐ muscle. These data demonstrated that the attenuation of denervation‐induced muscle wasting in accompanied by suppressed pro‐apoptotic signaling in skeletal muscle that is deficient of Bax. The present findings suggest that interventions targeting apoptosis may be valuable in ameliorating denervation‐associated pathologic muscle wasting in certain neuromuscular disorders. Supported by NIH R01AG021530.