Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment

Bodas, Manish; Westphal, Colin Van; Carpenter-Thompson, Rhett; Mohanty, Dillip K; Vij, Neeraj

doi:10.1016/j.freeradbiomed.2016.06.017

Cited by 104 publications

(101 citation statements)

References 61 publications

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“…Cigarette smoke is a major cause of COPD, and contains many oxidants, which are known to induce apoptosis 28. To clarify whether irisin can affect CSE-induced alveolar epithelial apoptosis through its antioxidant effect against cigarette smoking-induced oxidative stress, we conducted in vitro experiments using A549 cells.…”

Section: Discussionmentioning

confidence: 99%

Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease

Sugiyama

Asai

Yamada

et al. 2017

COPD

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BackgroundCigarette smoking-induced oxidant–antioxidant imbalance is a factor that contributes to the pathogenesis of COPD through epithelial cell apoptosis. Irisin is a skeletal muscle cell-derived myokine associated with physical activity. Irisin is also known to decrease oxidant-induced apoptosis in patients with diabetes mellitus. However, the correlation between irisin and emphysema in COPD and its role in epithelial cell apoptosis remains unknown.Subjects and methodsForty patients with COPD were enrolled in this study. Pulmonary function tests and measurements of the percentage of low-attenuation area on high-resolution computed tomography images were performed, and the results were evaluated for correlation with serum irisin levels. The effect of irisin on cigarette-smoke extract-induced A549 cell apoptosis and the expression of Nrf2, a transcription factor for antioxidants, was also examined in vitro.ResultsSerum irisin levels were significantly correlated with lung diffusing capacity for carbon monoxide divided by alveolar volume (r=0.56, P<0.01) and percentage of low-attenuation area (r=−0.79, P<0.01). Moreover, irisin significantly enhanced Nrf2 expression (P<0.05) and reduced cigarette-smoke extract-induced A549 cell apoptosis (P<0.05).ConclusionDecreased serum irisin levels are related to emphysema in patients with COPD and involved in epithelial apoptosis, resulting in emphysema. Irisin could be a novel treatment for emphysema in patients with COPD.

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Section: Discussionmentioning

confidence: 99%

Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease

Sugiyama

Asai

Yamada

et al. 2017

COPD

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“…These toxic ingredients are also present in other forms of indoor and outdoor air pollution, and can themselves activate redox pathways [13] that have also been implicated in acquired CFTR dysfunction [14]. In addition, unpublished data indicates that electronic cigarettes may cause acquire CFTR dysfunction in vitro.…”

Section: Acquired Cftr Dysfunction In Smoking-related Diseasesmentioning

confidence: 99%

The therapeutic potential of CFTR modulators for COPD and other airway diseases

Solomon

Rowe

et al. 2017

Current Opinion in Pharmacology

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Airways diseases, especially chronic obstructive pulmonary disease (COPD) and asthma, are common causes of morbidity and mortality worldwide. There is an ongoing unmet need for novel and effective therapies. There is an established pathophysiological link and phenotypic similarity between the chronic bronchitis phenotype of COPD and cystic fibrosis (CF). New evidence suggests that CFTR dysfunction may play a role in other common airways diseases such as COPD, non-atopic asthma and non-CF bronchiectasis. Newly approved and investigational drugs that target both mutant and wild type CFTR channels have provided a new treatment opportunity addressing the mucus defect in pulmonary diseases that share the same pathophysiology with CF.

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“…Exposure to tobacco and/or e-cig/nicotine vapor elevates oxidative-nitrative stress and inflammation that results in autophagy-flux impairment, further hampering the vital cellular homeostatic processes involved in the clearance of misfolded proteins and bacterial/viral pathogens that eventually impact the cell survival [10, 11, 18, 23–25]. Moreover, impaired autophagy flux results in perinuclear aggresome-bodies that are the hallmark of several neurodegenerative and protein-misfolding disorders [26–28].…”

Section: Introductionmentioning

confidence: 99%

“…The recent exhaustive studies using variety of pre-clinical models that includes human lung structural cells or tissues have clearly demonstrated that tobacco-smoke impaired-autophagy mediates accumulation of aggresome-bodies, which is primarily a cytoplasmic organelle comprised of aggregated (misfolded or damaged) proteins that initiates chronic inflammatory-apoptotic responses leading to senescence and emphysema progression (Fig. 1a) [10, 11, 17, 18, 20, 22, 25, 29, 30]. The pathogenic role of autophagy-impairment in COPD-emphysema is supported by findings from multiple studies demonstrating the accumulation of ubiquitinated proteins and p62 (an impaired-autophagy marker) that accelerates cellular senescence and COPD-emphysema pathogenesis [10, 11, 17, 18, 20, 22, 25, 29, 30].…”

Section: Introductionmentioning

confidence: 99%

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

Bodas

Vij

2017

Respir Res

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Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

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Nicotine exposure induces bronchial epithelial cell apoptosis and senescence via ROS mediated autophagy-impairment

Cited by 104 publications

References 61 publications

Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease

Decreased levels of irisin, a skeletal muscle cell-derived myokine, are related to emphysema associated with chronic obstructive pulmonary disease

The therapeutic potential of CFTR modulators for COPD and other airway diseases

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

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