Article (Scientific journals)
Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury
Quoilin, Caroline; Mouithys-Mickalad, Ange; Lécart, Sandrine et al.
2014In Biochimica et Biophysica Acta. Bioenergetics, 1837 (10), p. 1790-1800
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Keywords :
Sepsis; Acute kidney injury; Mitochondrial dysfunction; Cytopathic hypoxia; Oxidative stress; Nitric oxide
Abstract :
[en] To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal tubular epithelial cells exposed to a bacterial endotoxin (lipopolysaccharide, LPS). This investigation has provided key features on the relationship between oxidative stress and mitochondrial respiratory chain activity defects. LPS treatment resulted in an increase in the expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX-4), suggesting the cytosolic overexpression of nitric oxide and superoxide anion, the primary reactive nitrogen species (RNS) and reactive oxygen species (ROS). This oxidant state seemed to interrupt mitochondrial oxidative phosphorylation by reducing cytochrome c oxidase activity. As a consequence, disruptions in the electron transport and the proton pumping across the mitochondrial inner membrane occurred, leading to a decrease of the mitochondrial membrane potential, a release of apoptotic-inducing factors and a depletion of adenosine triphosphate. Interestingly, after being targeted by RNS and ROS, mitochondria became in turn producer of ROS, thus contributing to increase the mitochondrial dysfunction. The role of oxidants in mitochondrial dysfunction was further confirmed by the use of iNOS inhibitors or antioxidants that preserve cytochrome c oxidase activity and prevent mitochondrial membrane potential dissipation. These results suggest that sepsis-induced AKI should not only be regarded as failure of energy status but also as an integrated response, including transcriptional events, ROS signaling, mitochondrial activity and metabolic orientation such as apoptosis.
Research center :
Laboratoire de Spectroscopie Biomédicale
Disciplines :
Biochemistry, biophysics & molecular biology
Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others
Author, co-author :
Quoilin, Caroline ;  Université de Liège - ULiège > Département de physique > Spectroscopie biomédicale
Mouithys-Mickalad, Ange ;  Université de Liège - ULiège > Centre de l'oxygène : Recherche et développement (C.O.R.D.)
Lécart, Sandrine
Fontaine-Aupart, Marie-Pierre
Hoebeke, Maryse  ;  Université de Liège - ULiège > Département de physique > Spectroscopie biomédicale
Language :
English
Title :
Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury
Publication date :
October 2014
Journal title :
Biochimica et Biophysica Acta. Bioenergetics
ISSN :
0005-2728
eISSN :
1879-2650
Publisher :
Elsevier Science, Amsterdam, Netherlands
Volume :
1837
Issue :
10
Pages :
1790-1800
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
ULiège - Université de Liège [BE]
International Project of Scientific Cooperation (PICS No 5991) of the French National Center for Scientific Research (CNRS)
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since 17 August 2014

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