Increased proteolysis, myosin depletion, and atrophic AKT-FOXO signaling in human diaphragm disuse.

ABSTRACT:

Rationale

Patients on mechanical ventilation who exhibit diaphragm inactivity for a prolonged time (case subjects) develop decreases in diaphragm force-generating capacity accompanied by diaphragm myofiber atrophy.

Objectives

Our objectives were to test the hypotheses that increased proteolysis by the ubiquitin-proteasome pathway, decreases in myosin heavy chain (MyHC) levels, and atrophic AKT-FOXO signaling play major roles in eliciting these pathological changes associated with diaphragm disuse.

Methods

Biopsy specimens were obtained from the costal diaphragms of 18 case subjects before harvest (cases) and compared with intraoperative specimens from the diaphragms of 11 patients undergoing surgery for benign lesions or localized lung cancer (control subjects). Case

SUBMITTER: Levine S 

PROVIDER: S-EPMC3056225 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature