Protein Oxidation by Chronic Pulmonary Diseases in Children

Starosta, Vitaliy; Griese, Matthias

doi:10.1002/ppul.20289

Cited by 22 publications

(18 citation statements)

References 34 publications

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“…Most of the proteins undergoing significant increases in oxidation had decreases or very modest increases in levels of expression between young adults and aged rats. The susceptibility of some of these BAL proteins to oxidation has been reported previously in humans (53). We speculate that the increased oxidation of these proteins results in functional deficits in the aged rats.…”

Section: Discussionsupporting

confidence: 77%

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Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat

Umstead¹,

Freeman²,

Chinchilli³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Umstead TM, Freeman WM, Chinchilli VM, Phelps DS. Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat. Am J Physiol Lung Cell Mol Physiol 296: L14-L29, 2009. First published October 17, 2008 doi:10.1152/ajplung.90366.2008The incidence and severity of many lung diseases change with age. Some diseases, such as pneumonia, occur with increased frequency in children and the elderly. Proteins obtained by bronchoalveolar lavage (BAL) serve as the first line of defense against inhaled toxins and pathogens. Age-related changes in BAL protein expression and oxidative modification were examined in juvenile (1 mo), young adult (2 mo), and aged (18 mo) F344 rats using two-dimensional difference gel electrophoresis (2D-DIGE), matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-ToF/ToF) tandem mass spectrometry, and carbonyl immunoblotting. Using 2D-DIGE, we detected 563 protein spots, and MALDI-ToF/ToF identified 204 spots comprising 31 proteins; 21 changed significantly (17 increases) between juvenile and young adult or aged rats, but for 12 of these proteins, levels had a biphasic pattern, and levels in aged rats were less than in young adults. Relative carbonylation was determined by comparison of immunostaining with total protein staining on each oxidized protein blot. We found that aged rats had significantly increased oxidation in 13 proteins compared with juvenile rats. Many of the proteins altered in expression or oxidation level had functions in host defense, redox regulation, and protein metabolism. We speculate that low levels of expression of host defense proteins in juvenile rats and decreases in levels of these proteins between young adult and aged rats may predispose these groups to pneumonia. In addition, we have shown age-related increases in protein oxidation that may compromise host defense function in aged rats.aging; proteomics; host defense; carbonylation; proteolysis AGE IS A MAJOR FACTOR in the incidence of various lung diseases, particularly in the young and the old. Lung diseases, including chronic conditions such as emphysema and pulmonary fibrosis and acute lung diseases such as pneumonia, currently affect more than 35 million people in the U.S. Many of these diseases occur with increased frequency and severity in the elderly. However, pneumonia is also a serious problem in young children, both in developing countries, where it can be the leading cause of childhood mortality (48), and in developed countries, where morbidity is significant but mortality is low (16,43).Age also plays a role in how both humans and laboratory animals respond to pollution and various other insults. Aged organisms have an increased inflammatory response to oxidants, pollutants, and other insults (14,15,27,36,40) and are far more likely to become infected. Indeed, in the U.S., influenza and pneumonia are the fifth leading cause of death in patients over the age of 65 (37). Although it remains unclear why the elderly are more susceptible to pneumon...

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Section: Discussionsupporting

confidence: 77%

“…Several studies also have examined the carbonylation of BAL proteins in various diseases (47,53,54). However, no previous studies have examined changes in BAL protein expression or carbonylation with age.…”

Section: Ammentioning

confidence: 99%

Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat

Umstead¹,

Freeman²,

Chinchilli³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…A number of studies have shown that oxidation of SP-A by ozone impairs many aspects of SP-A function including decreased ability to interact with alveolar macrophages [15], to stimulate cytokine production by THP-1 cells [16 -17] to inhibit phosphatidylcholine (PC) and surfactant secretion by type II cells [18] and to stimulate TNF-a production by THP-1 cells in the presence of bleomycin [19]. In general, it has been found that SP-A was one of the most frequently oxidized lung proteins in children with chronic pulmonary diseases [20] as well as in patients with cystic fibrosis [21].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of ozone-induced SP-A oxidation by plant polyphenols

Stagos

Umstead

Phelps

et al. 2007

Free Radical Research

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Surfactant protein-A (SP-A) is the best studied and most abundant of the protein components of lung surfactant and plays an important role in host defense of the lung. It has been shown that ozone-induced oxidation of SP-A protein changes its functional and biochemical properties. In the present study, eight plant polyphenols (three flavonoids, three hydroxycinnamic acids, and two hydroxybenzoic acids) known as strong antioxidants, were tested for their ability to inhibit ozone-induced SP-A oxidation as a mechanism for chemoprevention against lung damage. SP-A isolated from alveolar proteinosis patients was exposed to ozone (1 ppm) for 4 h. The flavonoids protected SP-A from oxidation in a dose dependent manner. ( - )-Epicatechin was the most potent flavonoid and exhibited inhibition of ozone-induced formation of carbonyls by 35% at a concentration as low as 5 microM. Hydroxybenzoic acids inhibited SP-A oxidation in a dose-dependent manner although they were less potent than flavonoids. On the other hand, hydroxycinnamic acids exhibited a different inhibitory pattern. Inhibition was observed only at medium concentrations. The results indicate that inhibition of SP-A oxidation by plant polyphenols may be a mechanism accounting for the protective activity of natural antioxidants against the effects of ozone exposure on lungs.

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“…These triggers were severe gastro-intestinal reflux and pulmonary microaspiration, which were associated with declining lung function in infants and children [17], and reactive oxygen species-induced damage probably due to the depletion of glutathione, the major component of cell defences against oxidative injury, in the epithelial lining fluid and plasma of adults with CF [18][19][20].…”

Section: Lung Damage In Cystic Fibrosismentioning

confidence: 99%

Azithromycin use in patients with cystic fibrosis

Principi

Blasi

Esposito

2015

Eur J Clin Microbiol Infect Dis

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Rational antimicrobial administration is still considered to be the most effective therapeutic approach in cystic fibrosis (CF), and long-term treatment with azithromycin (Az) is included in the current guidelines for CF patients aged ≥ 6 years. Az has microbiological, immunomodulatory and anti-inflammatory properties that can reduce some of the biological problems that are among the causes of the progressive lung damage associated with CF. Moreover, although it is not active against Pseudomonas aeruginosa (the most important bacterial pathogen responsible for infectious exacerbations), it can be efficiently used in the case of P. aeruginosa infections because sub-inhibitory concentrations can reduce their pathogenic role by interfering with some bacterial activities and increasing their susceptibility to antibiotics. Az also has anti-viral activity that limits the risk of the bacterial pulmonary exacerbations that frequently occur after apparently mild viral infections. The available data seem to indicate that it is effective during its first year of administration, but the impact of longer treatment is debated. Other still undefined aspects of the use of Az include the possible emergence of antibiotic resistance in the other bacterial pathogens that usually colonise CF patients, the real incidence of adverse events and the drug's potential interference with other routine therapies.

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Protein Oxidation by Chronic Pulmonary Diseases in Children

Cited by 22 publications

References 34 publications

Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat

Age-related changes in the expression and oxidation of bronchoalveolar lavage proteins in the rat

Inhibition of ozone-induced SP-A oxidation by plant polyphenols

Azithromycin use in patients with cystic fibrosis

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