Oxidative Stress in COPD

Kirkham, Paul; Barnes, Peter J.

doi:10.1378/chest.12-2664

Cited by 602 publications

(505 citation statements)

References 75 publications

Supporting

Mentioning

452

Contrasting

Unclassified

Order By: Relevance

“…Despite the well-accepted contribution of oxidative stress to pulmonary emphysema, the efficacy of antioxidant therapy in pulmonary disease has been controversial (27,47), possibly because of genetic complexity in COPD patients. Given that Hhip +/− mice, which mimic human HHIP risk allele carriers with respect to HHIP expression levels, clearly derived more benefit from NAC treatment for pulmonary morphology and lung function improvement than Hhip +/+ mice, additional studies are needed to determine whether COPD patients carrying HHIP risk alleles benefit more from antioxidant therapies.…”

Section: Hhip Interacts With Gstp1 and Enhances Glutathione-conjugatingmentioning

confidence: 99%

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Lao

Jiang

Yun

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip+/−), we observed increased lung compliance and spontaneous emphysema in Hhip+/− mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip+/− vs. Hhip+/+ mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip+/− mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip+/− mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip+/− mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

show abstract

Section: Hhip Interacts With Gstp1 and Enhances Glutathione-conjugatingmentioning

confidence: 99%

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Lao

Jiang

Yun

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Indeed, oxidative stress has been long identified as a major factor behind CS-induced emphysematous lung damage, in which the possible involvement of cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been typically indicated (18)(19)(20). CS-induced oxidative stress releases inflammatory cytokines like IFN-γ, TNF-α, IL-1β, and IL-8, resulting in inflammatory lung damage by neutrophils and nuclear factor κB (NF-κB) (21,22) and the overexpression of inducible NOS (iNOS) and its product, nitric oxide (NO), contributing to extensive oxido-nitrosative lung damage (23,24).…”

mentioning

confidence: 99%

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

Gupta

Ganguly

Rozanas³

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxidonitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.cigarette smoke | emphysema | vitamin C | ascorbate | Rtp801

show abstract

“…In addition to emphasizing hypercapnia, for which a strategy is already defined in the international guidelines [31], chronic oxygen therapy can also accelerate oxidative injury. Hyperoxia can produce cellular injury through the production of ROS, which results in inflammation and cell death [82]. Recent studies have shown that supplemental oxygen increases the exhaled biomarkers of oxidative stress and airway inflammation [83].…”

Section: Future Researchmentioning

confidence: 99%

Domiciliary Oxygen: Facts and fallacies

Alvarado¹

2017

Clin Res Trial

View full text Add to dashboard Cite

Molecular oxygen is vital for energy which is essential for life. The fact that we all need oxygen to live might make us think that the use of supplemental oxygen in every hypoxemic patient seems obvious. This is a fallacy. The survival of all metazoan organisms is dependent on the regulation of the delivery and use of oxygen to maintain a balance between the generation of energy and the production of oxygen radicals, potentially toxic. HIF (hypoxia inducible factor) is a transcription factor or nuclear messenger that should be conceptualized as a master regulator of oxygen homeostasis. Therefore, it is proceeded to discuss how its action in hypoxia conditions the activation of diverse genes that codify the synthesis of proteins that explain some of the clinical manifestations and the events of hypoxia. We also discuss how inflammatory diseases of the respiratory system can perpetuate, in the presence of oxygen at inappropriately high doses, the oxidative stress that in turn amplifies the inflammatory phenomenon. Subsequently, the doses of ambulatory oxygen are defined in conventional indications and in some unconventional indications such as air travel and high altitude. Finally, some research avenues are mentioned in this topic.

show abstract

Oxidative Stress in COPD

Cited by 602 publications

References 75 publications

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Hhip haploinsufficiency sensitizes mice to age-related emphysema

Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

Domiciliary Oxygen: Facts and fallacies

Contact Info

Product

Resources

About