Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells

Wallaert, B.; Aerts, C; Gressier, Bernard; Gosset, Pierre; Voisin, C

doi:10.1152/jappl.1993.75.6.2376

Cited by 22 publications

(9 citation statements)

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“…To our knowledge, nothing like this has been described before in human pathology, and experimental and in vitro models are required to investigate this aspect further. It seems relevant that inactivation of ␣1AT by leukocytes has been reported extensively in the literature, this mechanism involving the production of free radicals from activated neutrophils and activation of specific proteases (27)(28)(29). This observation reinforces the hypothesis of a role of free radicals in nephrotic syndrome that has been proposed in the past but never received experimental support.…”

Section: Discussionsupporting

confidence: 81%

Repetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome

Candiano¹,

Musante²,

Bruschi³

et al. 2006

Journal of the American Society of Nephrology

136

107

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Even if nephrotic syndrome is characterized by massive urinary loss of major plasma proteins, a clear structural characterization based on proteomics has never been reported. Urine and plasma of 23 patients with different idiopathic nephrotic syndromes (10 steroid-sensitive minimal-change nephropathy, seven steroid-resistant FSGS, and six membranous glomerulonephritis) were analyzed with two-dimensional electrophoresis in soft gel, Western blot, and matrix-assisted laser desorption/ionization time of flight mass spectrometry; 72 urinary components corresponded to fragments of albumin and/or of ␣1-antitrypsin. Several repetitive fragmentation motives and a few differences among different pathologies were found. Several (21 of 72) urinary albumin fragments also were detected in plasma, although in lower concentration, suggesting a preferential excretion. The bulk of components with low molecular weight were detected only in urine, suggesting an in situ formation; zymograms with albumin as substrate showed the presence in urine of specific proteases. A final but not secondary point was the characterization of albumin adducts that harbor both the COOH and NH2 terminal parts of the protein, suggesting the formation of new covalent chemical groups. Altogether, these new findings reveal unexpected structural and functional aspects of proteinuria that may play a key role in pathogenesis. Characterization of urinary fragmentation patterns should be extended to other renal diseases.

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Section: Discussionsupporting

confidence: 81%

Repetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome

Candiano¹,

Musante²,

Bruschi³

et al. 2006

Journal of the American Society of Nephrology

136

107

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“…These include: (a) inducing MMP expression in other cells (via secretion of cytokines); (b) producing MMPs; and (c) activating latent forms of secreted MMPs (via production of reactive oxygen species). It is of note that antiprotease inhibitors (serpins) are susceptible to degradation by MMPs (55,56), possibly leading to an increase in proteolytic activity in the vicinity of activated macrophages. Similarly, activated neutrophils, which generate hypochlorous acid through the action of myeloperoxidase, seem capable of autoactivating their latent collagenase (57).…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.

Rajagopalan¹,

Meng²,

Ramasamy³

et al. 1996

J. Clin. Invest.

1,062

697

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Vulnerable areas of atherosclerotic plaques often contain lipid-laden macrophages and display matrix metalloproteinase activity. We hypothesized that reactive oxygen species released by macrophage-derived foam cells could trigger activation of latent proforms of metalloproteinases in the vascular interstitium. We showed that in vivo generated macrophage foam cells produce superoxide, nitric oxide, and hydrogen peroxide after isolation from hypercholesterolemic rabbits. Effects of these reactive oxygens and that of peroxynitrite, likely to result from simultaneous production of nitric oxide and superoxide, were tested in vitro using metalloproteinases secreted by cultured human vascular smooth muscle cells. Enzymes in culture media or affinitypurified (pro-MMP-2 and MMP-9) were examined by SDS-PAGE zymography, Western blotting, and enzymatic assays. Under the conditions used, incubation with xanthine/ xanthine oxidase increased the amount of active gelatinases, while nitric oxide donors had no noticeable effect. Incubation with peroxynitrite resulted in nitration of MMP-2 and endowed it with collagenolytic activity. Hydrogen peroxide treatment showed a catalase-reversible biphasic effect (gelatinase activation at concentrations of 4 M, inhibition at Ն 10-50 M). Thus, reactive oxygen species can modulate matrix degradation in areas of high oxidant stress and could therefore contribute to instability of atherosclerotic plaques. ( J. Clin. Invest. 1996. 98:2572-2579.)

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“…Other potential sites sensitive to the redox status are thiol sites critical for protein activity. The capacity of ␣ 1 -protease inhibitor to limit the proteolytic damage from neutrophil-derived elastase is attenuated by chronic oxidant stress (31,32). This inactivation of the ␣ 1 -protease inhibitor is modulated by GSH availability (33).…”

Section: Discussionmentioning

confidence: 99%

Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status

Yeh

Burnham²,

Moss³

et al. 2007

Am J Respir Crit Care Med

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Rationale: Previous studies have linked the development and severity of acute respiratory distress syndrome with a history of alcohol abuse. In clinical studies, this association has been centered on depletion of pulmonary glutathione and subsequent chronic oxidant stress. Objectives: The impact on redox potential of the plasma or pulmonary pools, however, has never been reported. Methods: Plasma and bronchoalveolar lavage fluid were collected from otherwise healthy alcohol-dependent subjects and control subjects matched by age, sex, and smoking history. Measurements and Main Results: Redox potential was calculated from measured reduced and oxidized glutathione in plasma and lavage. Among subjects who did and did not smoke, lavage fluid glutathione redox potential was more oxidized in alcohol abusers by approximately 40 mV, which was not altered by dilution. This oxidation of the airway lining fluid associated with chronic alcohol abuse was independent of smoking history. A shift by 20 mV in plasma glutathione redox potential, however, was noted only in subjects who both abused alcohol and smoked. Conclusions: Chronic alcoholism was associated with alveolar oxidation and, with smoking, systemic oxidation. However, systemic oxidation did not accurately reflect the dramatic alcohol-induced oxidant stress in the alveolar space. Although there was compensation for the oxidant stress caused by smoking in control groups, the capacity to maintain a reduced environment in the alveolar space was overwhelmed in those who abused alcohol. The significant alcohol-induced chronic oxidant stress in the alveolar space and the subsequent ramifications may be an important modulator of the increased incidence and severity of acute respiratory distress syndrome in this vulnerable population. Keywords: glutathione; alcoholism; oxidative stress; pulmonaryThe lungs are constantly exposed to environmental and endogenous oxidants. The ability to neutralize these oxidants is essential to maintain pulmonary health. There are major differences between cellular and extracellular compartments in concentration of the thiol/disulfide systems and the relative redox states. Since Cantin and colleagues' report, published in 1987, on the high glutathione (GSH) concentration in the airspace (more than 20-fold than that in the plasma and over 90% in the reduced form), GSH has been considered a primary antioxidant in the alveolar space (1). Although the alveolar space is exposed to the oxidants present in cigarette smoke, the alveolar GSH pool is increased by 80% with no significant oxidant stress, as evidenced by the

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Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar epithelial type II cells

Cited by 22 publications

References 0 publications

Repetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome

Repetitive Fragmentation Products of Albumin and α1-Antitrypsin in Glomerular Diseases Associated with Nephrotic Syndrome

Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability.

Chronic Alcoholism Alters Systemic and Pulmonary Glutathione Redox Status

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