Calcium Metabolism and Cystic Fibrosis: Mitochondrial Abnormalities Suggest a Modification of the Mitochondrial Membrane

Ruecker, Axel A Von; Bertele, R M; Harms, H. K.

doi:10.1203/00006450-198407000-00005

Cited by 39 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is possibly due to increased concentrations of oxidation products8 32 33 and a defect in intracellular oxygen metabolism 34. Glutathione, the major antioxidant in the lung, is reduced both in the epithelial lining fluid of the lung and in the plasma,4 possibly as a consequence of the basic genetic defect 4.…”

Section: Discussionmentioning

confidence: 99%

Increased carbon monoxide in exhaled air of patients with cystic fibrosis

Paredi¹,

Shah²,

Montuschi³

et al. 1999

Thorax

View full text Add to dashboard Cite

Background-Inflammation, oxidative stress, and recurrent pulmonary infections are major aggravating factors in cystic fibrosis. Nitric oxide (NO), a marker of inflammation, is not increased, however, probably because it is metabolised to peroxynitrite. Exhaled carbon monoxide (CO), a product of heme degradation by heme oxygenase 1 (HO-1) which is induced by inflammatory cytokines and oxidants, was therefore tested as a noninvasive marker of airway inflammation and oxidative stress. Methods-Exhaled CO and NO concentrations were measured in 29 patients (15 men) with cystic fibrosis of mean (SD) age 25 (1) years, forced expiratory volume in one second (FEV 1 ) 43 (6)%, 14 of whom were receiving steroid treatment. Results-The concentration of exhaled CO was higher in patients with cystic fibrosis (6.7 (0.6) ppm) than in 15 healthy subjects (eight men) aged 31 (3) years (2.4 (0.4) ppm, mean diVerence 4.3 (95% CI 2.3 to 6.1), p<0.001). Patients not receiving steroid treatment had higher CO levels (8.4 (1.0) ppm) than treated patients (5.1 (0.5) ppm, mean diVerence 3.3 (95% CI -5.7 to -0.9), p<0.01). Normal subjects had higher NO levels (6.8 (0.4) ppb) than patients with cystic fibrosis (3.2 (0.2) ppb, mean diVerence 3.8 (95% CI 2.6 to 4.9), p<0.05) and were not influenced by steroid treatment (3.8 (0.4) ppb and 2.7 (0.3) ppb for treated and untreated patients, respectively, mean diVerence 0.8 (95% CI -0.6 to 2.3), p>0.05). Patients homozygous for the F508 CFTR mutation had higher CO and NO concentrations than heterozygous patients (CO: 7.7 (1.8) ppm and 4.0 (0.6) ppm, respectively, mean diVerence 3.7 (95% CI -7.1 to -0.3), p<0.05; NO: 4.1 (0.5) ppb and 1.9 (0.7) ppb, respectively, mean diVerence 2.2 (95% CI -3.7 to -0.6), p<0.05). Conclusions-High exhaled CO concentrations in patients with cystic fibrosis may reflect induction of HO-1. Measurement of exhaled CO concentrations may be clinically useful in the management and monitoring of oxidation and inflammatory mediated lung injury. (Thorax 1999;54:917-920)

show abstract

Section: Discussionmentioning

confidence: 99%

Increased carbon monoxide in exhaled air of patients with cystic fibrosis

Paredi¹,

Shah²,

Montuschi³

et al. 1999

Thorax

View full text Add to dashboard Cite

show abstract

“…Calcium metabolism disorder is central to the pathology of CF (von Ruecker et al, 1984). Pulmonary fluid and nasal secretions in patients with CF contain elevated concentrations of Ca 2+ (Halmerbauer et al, 2000;Lorin et al, 1976).…”

Section: Introductionmentioning

confidence: 99%

Strain-specific proteome responses of Pseudomonas aeruginosa to biofilm-associated growth and to calcium

2007

View full text Add to dashboard Cite

Pseudomonas aeruginosa is an opportunistic pathogen that forms biofilms on mucous plugs in the lungs of cystic fibrosis (CF) patients, resulting in chronic infections. Pulmonary P. aeruginosa isolates often display a mucoid (alginate-producing) phenotype, whereas non-mucoid strains are generally associated with acute infections. We characterized the cytosolic proteomes of biofilm-associated and planktonic forms of a CF pulmonary isolate, P. aeruginosa FRD1, and a non-mucoid strain, PAO1. Since Ca 2+ metabolism is altered in CF pulmonary fluids, we also analysed the effect of Ca 2+ on the proteome responses of these strains. Both strains altered the abundances of 40-60 % of their proteins in response to biofilm growth and/or [Ca 2+ ].Differentially expressed proteins clustered into 12 groups, based on their abundance profiles. From these clusters, 146 proteins were identified by using MALDI-TOF/TOF mass spectrometry. Similarities as well as strain-specific differences were observed. Both strains altered the production of proteins involved in iron acquisition, pyocyanin biosynthesis, quinolone signalling and nitrogen metabolism, proteases, and proteins involved in oxidative and general stress responses. Individual proteins from these classes were highly represented in the biofilm proteomes of both strains. Strain-specific differences concerned the proteins within these functional groups, particularly for enzymes involved in iron acquisition and polysaccharide metabolism, and proteases. The results demonstrate that a mucoid CF isolate of P. aeruginosa responds to biofilm-associated growth and [Ca 2+ ] in a fashion similar to strain PAO1, but that strain-specific differences may allow this CF isolate to successfully colonize the pulmonary environment.

show abstract

“…They have also reported an increase in relative electron transport activity of mitochondrial complex in case of NADH-oxidase, NADH-cytochrome c reductase, and succinate-cytochrome c reductase in CF cells compared to control [18]. Altered levels of glutathione (GSH) and activity of glutathione reductase (GR) has been reported in CF compared to control [19,20].…”

Section: Mitochondrial Function and Cystic Fibrosis: Evidence In 1970mentioning

confidence: 93%

“…CF cells were also reported to show increase in the intracellular calcium concentration compared to control [16][17][18], moreover mitochondria showed enhanced calcium uptake [18]. They have also reported an increase in relative electron transport activity of mitochondrial complex in case of NADH-oxidase, NADH-cytochrome c reductase, and succinate-cytochrome c reductase in CF cells compared to control [18].…”

Section: Mitochondrial Function and Cystic Fibrosis: Evidence In 1970mentioning

confidence: 94%