NADPH oxidase activity is associated with cardiac osteopontin and pro-collagen type I expression in uremia.
Abstract Cardiovascular disease is a frequent complication inducing mortality in chronic kidney disease (CKD) patients, which can be determined by both traditional risk factors and non-traditional risk factors such as malnutrition and oxidative stress. This study aimed to investigate the role of oxidative stress in uremia-induced cardiopathy in an experimental CKD model. CKD was induced in Sprague-Dawley rats by a 4-week diet supplemented in adenine, calcium and phosphorous and depleted in proteins. CKD was associated with a 3-fold increase in superoxide anion production from the NADPH oxidase in the left ventricle, but the maximal activity of mitochondrial respiratory chain complexes was not different. Although manganese mitochondrial SOD activity decreased, total SOD activity was not affected and catalase or GPx activities were increased, strengthening the major role of NADPH oxidase in superoxide anion output. Superoxide anion output was associated with enhanced expression of osteopontin (×7.7) and accumulation of pro-collagen type I (×3.7). To conclude, the increased activity of NADPH oxidase during CKD is associated with protein modifications which could activate a pathway leading to cardiac remodelling.
UMR 204, Prévention des Malnutritions et des Pathologies Associées, IRD, University Montpellier 1 et 2, Montpellier, France.
Aurélie
A
Goux
Christine
C
Feillet-Coudray
Bernard
B
Jover
Gilles
G
Fouret
Anne-Sophie
AS
Bargnoux
Cécile
C
Cassan
Sylvain
S
Richard
Stéphanie
S
Badiou
Jean-Paul
JP
Cristol
D000225:Adenine / Q000009:adverse effects; D000818:Animals; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D004195:Disease Models, Animal; D004452:Echocardiography; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014511:Uremia / Q000097:blood; D000094765:Glutathione Peroxidase GPX1
D024042:Collagen Type I; D053495:Osteopontin; D013481:Superoxides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D000225:Adenine; D000094765:Glutathione Peroxidase GPX1