Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis

Toorn, Marco van der; Slebos, Dirk‐Jan; Bruin, Harold G. de; Leuvenink, Henri G. D.; Bakker, Stephan J. L.; Gans, Rijk O. B.; Koëter, Gerard H.; Oosterhout, Antoon J. M. van; Kauffman, Henk F.

doi:10.1152/ajplung.00291.2006

Cited by 133 publications

(110 citation statements)

References 43 publications

(46 reference statements)

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“…Higher CSE concentration or longer periods of stimulation with CSE leads to apoptosis or even necrosis, consistent with the results from other researchers [35,36]. Besides treatment factors, cell type [37] is also one factor that can affect cell apoptosis or necrosis when stimulated.…”

Section: Discussionsupporting

confidence: 91%

AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract

Chen

et al. 2011

Chin. Sci. Bull.

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An increasing body of evidence suggests that apoptosis of structural cells in the lung might be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). AP-2α is one of the important transcription factors involved in the modulation of apoptosis in carcinogenesis and idiopathic-dilated cardiomyopathy. The relationship between AP-2α and apoptosis in COPD remains to be elucidated. The aim of the present study was to investigate the expression of AP-2α in the lung tissues of rats with COPD induced by smoking and its possible protective effect on cigarette smoke extract (CSE) induced endothelial cell apoptosis. Sprague-Dawley rats (n = 24) were randomly assigned to normal and COPD groups. The COPD group was exposed to smoke from 20 commercial unfiltered cigarettes for 80 d before morphological assessment of the lung tissue was performed. The expression of AP-2α in lung tissues was measured by Western blotting. To demonstrate the relationship between apoptosis and AP-2α, in vitro cell experiments were carried out. Cells were treated with different concentrations of CSE before proliferation was measured by MTT. Apoptosis was then determined by Hoechst staining and the expression of cleaved caspase-3 and AP-2α by Western blotting over time following treatment with 5% CSE. Cells were then infected with an AP-2α adenovirus vector and the expression of cleaved caspase-3 and AP-2α was compared to the control groups by Western blotting. The COPD group showed larger air spaces and significant decrease of FEV 0.3 /FVC compared with the rats in the control group (P<0.05). The expression of AP-2α was significantly higher in the lung tissue of rats with COPD compared with those of controls (P<0.05). In the ECV304 cells, CSE induced apoptosis (P<0.01) and caspase-3 activation in a time-dependent manner and reduced the cell proliferation rate in a dose-dependent manner (P<0.005). Moreover, 5% CSE treatment increased endogenous AP-2α protein expression. AP-2α overexpression inhibited 5% CSE-induced cell apoptosis and activated caspase-3 expression (P<0.05) AP-2α protects ECV304 cells against CSE-induced apoptosis and may play an important role in smoking induced-apoptosis in COPD. AP-2α, apoptosis, cigarette smoke extract, COPD, vascular endothelial cell Citation:Li J L, Chen Y, Chen P, et al. AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract. Chinese Sci Bull, 2011Bull, , 56: 1562Bull, −1568Bull, , doi: 10.1007 Chronic obstructive pulmonary disease (COPD) is one of the major public health problems because of its high morbidity and mortality, but its pathogenesis remains enigmatic.

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Section: Discussionsupporting

confidence: 91%

AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract

Chen

et al. 2011

Chin. Sci. Bull.

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“…Consistent with our current findings, van der Toorn et al, showed that CSE blocks the mitochondrial respiratory chain and ATP production in lung fibroblasts. 19 Thus, CSE exposure should drive hTERT-BJ1 fibroblasts toward glycolysis and ketogenesis. As predicted, we observed that CSE-treated fibroblasts displayed a significant increase in L-lactate and ketone production.…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment

et al. 2013

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“…Previous studies show that muscle mitochondrial function is altered in patients with COPD (31,118,133,164), and that CS induces rapid depolarization of mitochondrial membrane potential in human pulmonary and bronchial epithelial cells with loss of cellular ATP (163,177). As a damage control mechanism, mitophagy may be activated in response to CS exposure.…”

Section: Figmentioning

confidence: 99%

Autophagy: A Crucial Moderator of Redox Balance, Inflammation, and Apoptosis in Lung Disease

Nakahira

Cloonan

Mizumura

et al. 2014

Antioxidants & Redox Signaling

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Significance: Autophagy is a fundamental cellular process that functions in the turnover of subcellular organelles and protein. Activation of autophagy may represent a cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Autophagy can increase survival during nutrient deficiency and play a multifunctional role in host defense, by promoting pathogen clearance and modulating innate and adaptive immune responses. Recent Advances: Autophagy has been described as an inducible response to oxidative stress. Once believed to represent a random process, recent studies have defined selective mechanisms for cargo assimilation into autophagosomes. Such mechanisms may provide for protein aggregate detoxification and mitochondrial homeostasis during oxidative stress. Although long studied as a cellular phenomenon, recent advances implicate autophagy as a component of human diseases. Altered autophagy phenotypes have been observed in various human diseases, including lung diseases such as chronic obstructive lung disease, cystic fibrosis, pulmonary hypertension, and idiopathic pulmonary fibrosis. Critical Issues: Although autophagy can represent a pro-survival process, in particular, during nutrient starvation, its role in disease pathogenesis may be multifunctional and complex. The relationship of autophagy to programmed cell death pathways is incompletely defined and varies with model system. Future Directions: Activation or inhibition of autophagy may be used to alter the progression of human diseases. Further resolution of the mechanisms by which autophagy impacts the initiation and progression of diseases may lead to the development of therapeutics specifically targeting this pathway. Antioxid. Redox Signal. 20,

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Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches lung epithelial cell apoptosis into necrosis

Cited by 133 publications

References 43 publications

AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract

AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract

Cigarette smoke metabolically promotes cancer, via autophagy and premature aging in the host stromal microenvironment

Autophagy: A Crucial Moderator of Redox Balance, Inflammation, and Apoptosis in Lung Disease

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