Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation

Haikel Dridi; Mohamad Yehya; Robert J. Barsotti; Steven Reiken; Claire Angebault; Boris Jung; Samir Jaber; Andrew R Marks; Alain Lacampagne; Stephan Matecki

Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation

Haikel Dridi, Mohamad Yehya, Robert J. Barsotti, Steven Reiken, Claire Angebault, Boris Jung, Samir Jaber, Andrew R Marks, Alain Lacampagne, Stephan Matecki

Department of Bio-Medical Sciences (PCOM)

Research output: Contribution to journal › Article › peer-review

Abstract

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

Original language	American English
Journal	Free Radical Biology and Medicine
State	Published - Nov 19 2019

Keywords

Calcium homeostasis
Diaphragm contractile function
Mitochondrial oxidative stress

Disciplines

Medicine and Health Sciences

Cite this

@article{4b6506a83c564e41ad6edfc3e84d1689,

title = "Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation",

abstract = " 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",

keywords = "Calcium homeostasis, Diaphragm contractile function, Mitochondrial oxidative stress",

author = "Haikel Dridi and Mohamad Yehya and Barsotti, {Robert J.} and Steven Reiken and Claire Angebault and Boris Jung and Samir Jaber and Marks, {Andrew R} and Alain Lacampagne and Stephan Matecki",

year = "2019",

month = nov,

day = "19",

language = "American English",

journal = "Free Radical Biology and Medicine",

}

TY - JOUR

T1 - Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation

AU - Dridi, Haikel

AU - Yehya, Mohamad

AU - Barsotti, Robert J.

AU - Reiken, Steven

AU - Angebault, Claire

AU - Jung, Boris

AU - Jaber, Samir

AU - Marks, Andrew R

AU - Lacampagne, Alain

AU - Matecki, Stephan

PY - 2019/11/19

Y1 - 2019/11/19

N2 - 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

AB - 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

KW - Calcium homeostasis

KW - Diaphragm contractile function

KW - Mitochondrial oxidative stress

UR - https://digitalcommons.pcom.edu/scholarly_papers/2027

M3 - Article

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -

Mitochondrial Oxidative Stress Induces Leaky Ryanodine Receptor During Mechanical Ventilation

Abstract

Keywords

Disciplines

Other files and links

Cite this