Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein

Lam, C.C.; Casanova, Mercedes; Heck, Henry d’A.

doi:10.1007/bf00348311

Cited by 73 publications

(34 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These changes were most prominent on the septum and in the anterior and ventral areas. Exposure to acrolein also produces a concentration-dependent decrease in the nonprotein sulfhydryl concentration in the nasal respiratory mucosa (244). Similar results were obtained by Feron and Kyrusee in 1978 in inhalation tests on hamsters and rabbits (241).…”

Section: Experimental Studiessupporting

confidence: 68%

Aldehydes and Acetals

Borchers¹

2012

Patty's Toxicology

View full text Add to dashboard Cite

More than 300 aldehydes occur in foods, water, and air. Due to the electrophilicity of the carbonyl carbon, particularly when proximal to a carbon–carbon double bond, aldehydes react with thiols and amines to form protein–protein, DNA–protein, and DNA–DNA cross‐links. Despite their potential for causing cell damage, toxicological and exposure data for a large number of aldehydes are lacking. Inhalation and ingestion studies have demonstrated that a number of aldehydes are irritants and can induce tumors in animal models. Formaldehyde, which is a suspected carcinogen, is the most widely studied of these compounds. The physicochemical properties of saturated aldehydes are summarized. Toxicological and health effects are given.

show abstract

Section: Experimental Studiessupporting

confidence: 68%

Aldehydes and Acetals

Borchers¹

2012

Patty's Toxicology

View full text Add to dashboard Cite

show abstract

“…Inhalation of acrolein is known to induce changes in airway structure and function in rats, possibly through depletion of GSH and inhibition of the various GSH redox enzymes in the rat nasal mucosa [53,54] and in alveolar A549 epithelial cells in vitro [55]. Acrolein (2 ppm) exposure to rats causes bronchioles to be filled with desquamised cells along with isolated peribronchial monocytes [56].…”

Section: Acroleinmentioning

confidence: 99%

Oxidative stress and redox regulation of lung inflammation in COPD

Rahman

Adcock²

2006

Eur Respir J

783

599

View full text Add to dashboard Cite

Reactive oxygen species, either directly or via the formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (cJun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-kB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-kBmediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of kB-a kinase or the enhanced recruitment and activation of transcriptional coactivators. Enhanced NF-kB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression.Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity.The antioxidant/anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-cysteine and N-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/ quercetin and reserveratol), specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-kB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells.Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.

show abstract

“…Acrolein can act directly as an electrophilic compound to deplete nonprotein sulfhydryl groups/glutathione in the respiratory epithelium (146,147) or to inactivate metabolizing enzymes (148,149). Despite limited knowledge about cisactivating and trans-activating elements regulating MUC5AC expression, electrophiles are known to activate gene expression via a mechanism involving glutathione depletion and the production of ROS (150).…”

Section: Smoke-induced Mucin Expressionmentioning

confidence: 99%

Mucin Overproduction in Chronic Inflammatory Lung Disease

Hauber

Foley

Hamid

2006

Canadian Respiratory Journal

View full text Add to dashboard Cite

H-P Hauber, SC Foley, Q Hamid. Mucin overproduction in chronic inflammatory lung disease. Can Respir J 2006;13(6):327-335.Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed.Key Words: Bacteria; Cytokine; Lung; Mucin; Neutrophil elastase; Overproduction; Smoke La surproduction de mucine dans la pneumopathie inflammatoire chronique La surproduction de mucus et l'hypersécrétion sont courantes en présence d'une pneumopathie inflammatoire chronique. Les mucines sont des glycoprotéines gélifiantes qui peuvent être stimulées par divers médiateurs. La présente analyse traite des mécanismes de régulation positive des mucines sécrétées. Est également exposée l'induction des mucines par l'élastase des neutrophiles, les bactéries, les cytokines, les facteurs de croissance, la fumée et la défaillance du régulateur de conductance transmembraneuse de la fibrose kystique. M ucus is an important component of both the physiological and pathological processes in airways. It protects, moisturizes and lubricates mucosal surfaces, and traps bacteria and other inhaled irritants for removal by mucociliary clearance. However, excessive production of airway mucus is a feature of chronic inflammatory lung diseases such as bronchial asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cystic fibrosis (CF). Mucus hypersecretion results from hyperplasia and metaplasia of mucous cells, which lead to greater numbers of these cells being found throughout the airways, including the distal airways, where they are normally absent (1). The presence of neutrophil elastase, certain bacterial pathogens and altered cytokine patterns all contribute to excess airway mucus production. This overproduction and hypersecretion of mucus, in turn, contributes to airway obstruction and impairment of mucociliary clearance.An understanding of the mechanisms that lead to mucus overproduction and secretion is therefore of great clinical interest. The present review provides insight into the mechanisms by which excessive mucus production is stimulated in chronic inflammatory lung disease, focusing mainly on enhanced gene expression and protein production of secretory mucins in the airways. MUCINSMucus is formed within the airways by a polymeric matrix of large, oligomeric, gel-forming glycoproteins, called mucins. These gel-forming mucins are primarily responsible for the rheological properties of airway mucus (2). However, in disease states such as CF and chronic bronchitis, polymeric DNA and filamentous actin, two products of leukocyte lysis, contribute greatly to, and are the principal determinants of, the viscoelastic properties of the purulent sputum...

show abstract

Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein

Cited by 73 publications

References 21 publications

Aldehydes and Acetals

Aldehydes and Acetals

Oxidative stress and redox regulation of lung inflammation in COPD

Mucin Overproduction in Chronic Inflammatory Lung Disease

Contact Info

Product

Resources

About