Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation
RATIONALE: Ventilator-induced diaphragm dysfunction (VIDD) increases morbidity and mortality in critical care patients. Although VIDD has been associated with mitochondrial oxidative stress and calcium homeostasis impairment, the underling mechanisms are still unknown. We hypothesized that diaphragmatic mitochondrial oxidative stress causes remodeling of the ryanodine receptor (RyR1)/calcium release channel, contributing to sarcoplasmic reticulum (SR) Ca
METHOD: In mice diaphragms mechanically ventilated for short (6 h) and long (12 h) period, we assessed mitochondrial ROS production, mitochondrial aconitase activity as a marker of mitochondrial oxidative stress, RyR1 remodeling and function, Ca
MEASUREMENTS AND MAIN RESULTS: 6 h of mechanical ventilation (MV) resulted in increased mitochondrial ROS production, reduction of mitochondrial aconitase activity, increased oxidation, S-nitrosylation, S-glutathionylation and Ser-2844 phosphorylation of RyR1, depletion of stabilizing subunit calstabin1 from RyR1, increased SR Ca
Free Radical Biology and Medicine
Dridi, Haikel; Yehya, Mohamad; Barsotti, Robert J.; Reiken, Steven; Angebault, Claire; Jung, Boris; Jaber, Samir; Marks, Andrew R; Lacampagne, Alain; and Matecki, Stephan, "Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation" (2019). PCOM Scholarly Papers. 2027.