Antioxidant Status in Patients with Cystic Fibrosis

Madarasi, Anna; Lugassi, A; Greiner, Erika; Holics, K; Biró, Lajos; Mozsáry, Erzsébet

doi:10.1159/000046685

Cited by 23 publications

(7 citation statements)

References 27 publications

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“…By the contrary, a decrease in the activity of extracellular SOD (EC-SOD/SOD3) was observed in CF cells, without changes in its protein expression level [192]. These results are in agreement with previous work in which a decrease in the SOD activities was found in plasma of CF patients [221]. They are also in agreement with a decrease in the Cu/Zn-SOD activity of blood cells (mononuclear cells and polymorphonuclear cells) from CF patients [222,223].…”

Section: Diverse Processes Affected In Cf and Related To Mitochondriasupporting

confidence: 92%

CFTR activity and mitochondrial function

Valdivieso

Santa‐Coloma

2013

Redox Biology

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Cystic Fibrosis (CF) is a frequent and lethal autosomal recessive disease, caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Before the discovery of the CFTR gene, several hypotheses attempted to explain the etiology of this disease, including the possible role of a chloride channel, diverse alterations in mitochondrial functions, the overexpression of the lysosomal enzyme α-glucosidase and a deficiency in the cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse mitochondrial changes found, some authors proposed that the affected gene should codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration of its chloride channel activity turned the mitochondrial, lysosomal and cytosolic hypotheses obsolete. However, in recent years, using new approaches, several investigators reported similar or new alterations of mitochondrial functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria in this disease. Here, we review these CFTR-driven mitochondrial defects, including differential gene expression, alterations in oxidative phosphorylation, calcium homeostasis, oxidative stress, apoptosis and innate immune response, which might explain some characteristics of the complex CF phenotype and reveals potential new targets for therapy.

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Section: Diverse Processes Affected In Cf and Related To Mitochondriasupporting

confidence: 92%

CFTR activity and mitochondrial function

Valdivieso

Santa‐Coloma

2013

Redox Biology

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“…Thus, although an insufficient expression of SODs could account for an increased level of O 2 − , it is most likely that the reduction in EC-SOD activity plays an essential role in the elevation on O 2 − levels. In agreement with the present results, Madarasi et al [35] have shown that in plasma from patients with CF, SOD activities were significantly lower when compared with healthy subjects. Also, reduced activity of Cu/Zn-SOD has been described in mononuclear, polymorphonuclear and red cells in CF patients [36], [37].…”

Section: Discussionsupporting

confidence: 94%

Increased Oxidative Stress Induces Apoptosis in Human Cystic Fibrosis Cells

et al. 2011

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Oxidative stress results in deleterious cell function in pathologies associated with inflammation. Here, we investigated the generation of superoxide anion as well as the anti-oxidant defense systems related to the isoforms of superoxide dismutases (SOD) in cystic fibrosis (CF) cells. Pro-apoptotic agents induced apoptosis in CF but not in control cells that was reduced by treatment with SOD mimetic. These effects were associated with increased superoxide anion production, sensitive to the inhibition of IκB-α phosphorylation, in pancreatic but not tracheal CF cells, and reduced upon inhibition of either mitochondrial complex I or NADPH oxidase. CF cells exhibited reduced expression, but not activity, of both Mn-SOD and Cu/Zn-SOD when compared to control cells. Although, expression of EC-SOD was similar in normal and CF cells, its activity was reduced in CF cells. We provide evidence that high levels of oxidative stress are associated with increased apoptosis in CFTR-mutated cells, the sources being different depending on the cell type. These observations underscore a reduced anti-oxidant defense mechanism, at least in part, via diminished EC-SOD activity and regulation of Cu/Zn-SOD and Mn-SOD expressions. These data point to new therapeutic possibilities in targeting anti-oxidant pathways to reduce oxidative stress and apoptosis in CF cells.

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“…In another report on vitamin E status in infants diagnosed by newborn screening, of the initial patients who were vitamin E sufficient, 12% subsequently became deficient despite supplementation, and 10% remained persistently deficient [107]. Numerous studies have shown that the great majority of children and adults with CF who do not receive vitamin E supplementation are deficient in vitamin E, even if they receive standard multiple vitamins and are on pancreatic replacement enzymes [107,108]. Unfortunately, no lung tissue or airway secretion determinations of vitamin E levels have been made in people with CF.…”

Section: Vitamin E (α-Tocopherol)mentioning

confidence: 99%

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

Cantin

White

Cross

et al. 2007

Free Radical Biology and Medicine

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Although great strides are being made in the care of individuals with cystic fibrosis (CF), this condition remains the most common fatal hereditary disease in North America. Numerous links exist between progression of CF lung disease and oxidative stress. The defect in CF is the loss of function of the transmembrane conductance regulator (CFTR) protein; recent evidence that CFTR expression and function are modulated by oxidative stress suggests that the loss may result in a poor adaptive response to oxidants. Pancreatic insufficiency in CF also increases susceptibility to deficiencies in lipophilic antioxidants. Finally the airway infection and inflammatory processes in the CF lung are potential sources of oxidants that can affect normal airway physiology and contribute to the mechanisms causing characteristic changes associated with bronchiectasis and loss of lung function. These multiple abnormalities in the oxidant/antioxidant balance raise several possibilities for therapeutic interventions that must be carefully assessed. IntroductionCystic fibrosis (CF) is the most common fatal disease caused by a single gene defect in Europe and North America [1,2]. The defective gene was identified in 1989 [3][4][5] and shown to encode the cystic fibrosis trans-membrane conductance regulator protein (CFTR). CFTR is a cyclic AMP-regulated anion channel with greatest selectivity for chloride, and bicarbonate [6][7][8]. Furthermore, CFTR regulates sodium transport across epithelial membranes through interactions with the epithelial sodium channel ENaC [9], and facilitates the trans-membrane export of the small organic anionic peptide glutathione [10]. The expression of CFTR is located in the apical membrane of epithelial cells that line mucous membranes and submucosal glands ☆ A list of participants may be found in the Acknowledgments.

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Antioxidant Status in Patients with Cystic Fibrosis

Cited by 23 publications

References 27 publications

CFTR activity and mitochondrial function

CFTR activity and mitochondrial function

Increased Oxidative Stress Induces Apoptosis in Human Cystic Fibrosis Cells

Antioxidants in cystic fibrosis☆Conclusions from the CF Antioxidant Workshop, Bethesda, Maryland, November 11-12, 2003

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