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HSP72 is required for exercise‐induced protection against ventilator‐induced diaphragm dysfunction
Author(s) -
Smuder Ashley J,
Morton Aaron B,
Hall Stephanie E,
Ahn Bumsoo,
Wiggs Michael P,
Wawrzyniak Nicholas R,
Powers Scott K
Publication year - 2016
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.30.1_supplement.769.2
Subject(s) - diaphragm (acoustics) , medicine , endurance training , skeletal muscle , atrophy , heat shock protein , diaphragm muscle , oxidative stress , endocrinology , reactive oxygen species , cardiology , respiratory system , biology , microbiology and biotechnology , biochemistry , gene , physics , acoustics , loudspeaker
Mechanical ventilation (MV) is a life‐saving measure for patients in respiratory failure. However, prolonged MV causes significant diaphragm atrophy and contractile dysfunction, a condition referred to as ventilator‐induced diaphragm dysfunction (VIDD). VIDD occurs as a result of mitochondrial dysfunction, which triggers the production of reactive oxygen species (ROS) and initiates proteolysis. Recent evidence reveals that endurance exercise training is sufficient to prevent MV‐induced mitochondrial dysfunction and avert VIDD. However, the mechanism by which exercise protects the diaphragm against VIDD remains unknown. It is established that exercise promotes numerous cytoprotective adaptations in skeletal muscle fibers, including increased expression of heat shock protein 72 (HSP72). HSP72 plays a key role in numerous cellular functions and overexpression of HSP72 in skeletal muscle can protect against inactivity‐induced muscle atrophy. Therefore, we tested the hypothesis that exercise‐induced HSP72 expression is required to protect against VIDD. Cause and effect was determined by inhibiting the endurance exercise‐induced increase in HSP72 in the diaphragm of exercise trained animals that were subsequently exposed to prolonged MV. Our results confirm that exercise training protects against MV‐induced mitochondrial dysfunction and ROS production, and prevents VIDD. Importantly, inhibition of the exercise‐induced increase in HSP72 in the diaphragm precluded the exercise‐induced protection against VIDD. In addition, prevention of exercise‐induced increases in diaphragm HSP72 attenuated the exercise‐induced reduction in MV‐induced mitochondrial dysfunction, ROS production and protease activation in the diaphragm. We conclude that exercise‐induced protection against VIDD is mediated, in part, by increased abundance of HSP72 in the diaphragm. Support or Funding Information Supported by NIH R01 AR064189 awarded to SKP