Cigarette smoke extract regulates cytosolic phospholipase A<sub>2</sub> expression via NADPH oxidase/MAPKs/AP‐1 and p300 in human tracheal smooth muscle cells

Cheng, Shin Ei; Lin, Chih Chung; Lee, I-Te; Hsu, Chih Kai; Kou, Yu Ru; Yang, Che‐Hua

doi:10.1002/jcb.22949

Cited by 26 publications

(27 citation statements)

References 44 publications

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“…Our data indicate that CSE and NNK stimulate NAD(P)H oxidase in pancreatic ductal cells. This is in accord with the publications on other cells demonstrating stimulation of NAD(P)H oxidase by smoking compounds (33;34). We showed before that ROS produced by NADPH oxidase stimulate Akt phosphorylation resulting in suppression of cell death in pancreatic cancer cells (27;35).…”

Section: Discussionsupporting

confidence: 93%

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Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Park¹,

Lee²,

Grippo³

et al. 2013

Pancreas

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Objectives Cigarette smoking is a major risk factor for pancreatic cancer (PaCa). However, the mechanisms of smoking-induced PaCa remain unknown. Here we investigated the effect of smoking compounds on cell death pathways in pancreatic ductal cells, precursors of PaCa. Methods Human pancreatic ductal cells (HPDE6-c7) were cultured with cigarette smoking extract (CSE) or smoking compound 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Apoptosis and autophagy were assessed by DNA fragmentation and immunofluorescence, respectively. Results Exposure to CSE or NNK decreased DNA fragmentation and up-regulated BclxL. Akt kinase was activated by smoking compounds through ROS-dependent mechanism. Specifically, Akt activation was prevented by inhibition of NAD(P)H oxidase. Molecular or pharmacologic inhibitions of Akt prevented anti-apoptotic effect of smoking compounds. Smoking compounds stimulated rapid (1h) and transient activation of AMPK and formation of autophagic vacuoles indicating stimulation of autophagy. Repeated exposure to CSE/NNK (48h or longer) abolished the early activation of autophagic markers. Inhibition of Akt prevented the anti-autophagic effect of long exposure to smoking compounds indicating that smoking-induced late activation of Akt prevents autophagy. Conclusions long exposure of pancreatic ductal cells to smoking compounds inhibited apoptosis and autophagy. The results revealed a central role for Akt kinase in mediating key pro-carcinogenic effects of smoking compounds.

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Section: Discussionsupporting

confidence: 93%

“…In fact, oxidative stress induced by CSE and NNK (33;34) has been shown to inhibit creatine kinase in different cells leading to a decrease in the ATP/AMP ratio and therefore, leading to the activation of AMPK (37;38). …”

Section: Discussionmentioning

confidence: 99%

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Park¹,

Lee²,

Grippo³

et al. 2013

Pancreas

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“…In fact, recent reports have shown that all these pathways are involved in CSE-induced ETB and ETA expression in rat basilar arteries [9,10]. Furthermore, both CSE and ET-1 activate the reduced nicotinamide adenine dinucleotide phosphate oxidase complex to produce intracellular ROS [31,32]. Interestingly, both the CSE oxygen species H 2 O 2 and ET-1-induced intracellular ROS are mediated by the activation of ETA, since it has been shown that BQ123 inhibits them in fetal PASMCs [32].…”

Section: Discussionmentioning

confidence: 97%

Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries

Milara

Gabarda²,

Juan³

et al. 2011

Eur Respir J

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The endothelin (ET) system contributes to lung vascular tension and remodelling in smokers and chronic obstructive pulmonary disease (COPD) patients.This study examined the effect of cigarette smoke (CS) on ET receptor A (ETA) and B (ETB) expression in human pulmonary artery smooth muscle cells (HPASMCs) and human small intrapulmonary arteries, as well as their functional consequences.CS extract (CSE) increased ETA and ETB expression in HPASMCs and small intrapulmonary arteries, which was attenuated by bosentan, the ETA antagonist BQ123 and the ETB antagonist BQ788, and by blocking ET-1 with a monoclonal antibody against ET-1, suggesting a feed-forward mechanism mediated by ET-1 release. ET receptor (ETR) antagonism attenuated the CSE-induced HPASMC proliferation. Furthermore, CSE exposure increased the acute ET-1-induced small intrapulmonary artery contraction, which was attenuated by bosentan, BQ123 and BQ788. Pulmonary arteries from smokers and COPD patients showed a higher expression of ETA and ETB than those of nonsmoker patients.These results show a novel mechanism by which ETR blockade attenuates CS-induced ETR overexpression and, subsequently, small intrapulmonary artery tension. These data may be of potential value to explain therapeutic effects of bosentan in some forms of disproportionate pulmonary hypertension in COPD patients.KEYWORDS: Bosentan, cigarette smoke, endothelin receptor, human pulmonary artery smooth muscle cells, precision-cut lung slice P ulmonary hypertension (PH) is a relatively common form of cigarette smoke (CS)-induced lung disease. PH develops in ,6% of subjects with chronic obstructive pulmonary disease (COPD) but is present in ,40% of patients with a forced expiratory volume in 1 s of ,1 L [1, 2]. The pathogenesis of PH in COPD is unclear. Current studies suggest that PH is caused by the direct effects of CS on the intrapulmonary vessels by the secretion of a number of vasoconstrictive/proliferative peptides, such as endothelin (ET) or vascular endothelial growth factor, which subsequently contribute to vascular remodelling and the development of PH [3]. The circulating levels of ET-1 are elevated after exposure to CS in humans [4] and it has been shown that ET-1 correlates with pulmonary systolic pressure in COPD patients with PH [5], suggesting that ET-1 is involved in CS-induced vascular remodelling. ET-1 activates two receptors, ETA and ETB, which are located in pulmonary artery smooth muscle cells (PASMCs), whilst exclusively ETB are present in endothelial cells. Both ETA and ETB mediate proliferation and contractility in PASMCs from small pulmonary arteries, while endothelial ETB mediates vasodilation in normal pulmonary arteries. ETB upregulation has been observed in human blood vessels from patients with ischaemic heart disease [6], hypertension [7] and severe PH [8]. More recently, it has been shown that CS extract (CSE) induces ETA and ETB overexpression in resistant cerebral arteries from rats by a mechanism implicating the activation of the intracellular m...

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“…Moreover, we found that there were gene-environment interactions between PIN1 c.-842C variant genotypes and smoking as the protective role of c.-842C variant genotypes were more significant in smokers, especially in current smokers and male smokers, than in never smokers. As we know, cigarette smoking is the most common environmental risk factor of lung cancer [Spitz et al, 2007] and a stimulus of oncogenic phosphorylation signal pathway [Cheng et al, 2011]. The finding of c.-842C variant genotypes in decreasing the transcription of the PIN1 gene might lead to reduced oncogenic phosphorylation signals and thus reduce the cancer risk.…”

Section: Discussionmentioning

confidence: 99%

“…32, No. 11, 1299-1308, 2011 Figure 2. Abolishment of potent nuclear extract binding site in the PIN1 promoter by the c.-842G>C change.…”

Section: Nuclear Proteins Binding With Probes Containing Pin1 C-842gmentioning

confidence: 99%

The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in southern and eastern chinese populations

et al. 2011

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Peptidyl-prolyl cis/trans isomerase (PPIase), PIN1, has been found to be a critical catalyst that involves in multiple oncogenic signaling pathways. Recently, several putative functional polymorphisms of the PIN1 gene have been identified to be associated with cancer risk. In this study, we tested the hypothesis that two common polymorphisms, c.-842G>C (rs2233678) and c.-667C>T (rs2233679), in the PIN1 promoter are associated with risk of lung cancer. In two independent case-control studies of 1,559 lung cancer cases and 1,679 controls conducted in Southern and Eastern Chinese population, we found that compared with the most common c.-842GG genotype, the carriers of c.-842C variant genotypes (GC + CC) had a decreased risk of lung cancer (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.51-0.78, p = 1.13 × 10(-5) ). Although no association was observed between the c.-667C>T polymorphism and cancer risk, we found that the haplotype "C-C" had a greater protective effect (OR = 0.39, 95% CI = 0.23-0.67, p = 5.03 × 10(-4) ). The stratification analysis showed that the protective role of c.-842C variants was more pronounced in current smokers (p = 4.45 × 10(-5) ), especially in male smokers (p = 6.71 × 10(-6) ) and in those who smoked more than 20 pack-years (p = 2.30 × 10(-5) ) and the c.-842C variant genotypes interacted with smoking status (P(interaction) = 0.019) or pack-years smoked (P(interaction) = 0.008) on reducing cancer risk. Further functional assay revealed that the c.-842C variant allele had a lower transcription activity in luciferase assay and a lower DNA-binding ability with nuclear proteins, and low transcription activity in western blot assay. In conclusions, our data suggest that functional c.-842C variants and haplotype "C-C" in the PIN1 promoter contribute to decreased risk of lung cancer by diminishing the promoter activity, which may be susceptibility biomarkers for lung cancer.

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Cigarette smoke extract regulates cytosolic phospholipase A₂ expression via NADPH oxidase/MAPKs/AP‐1 and p300 in human tracheal smooth muscle cells

Cited by 26 publications

References 44 publications

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries

The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in southern and eastern chinese populations

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Cigarette smoke extract regulates cytosolic phospholipase A2 expression via NADPH oxidase/MAPKs/AP‐1 and p300 in human tracheal smooth muscle cells

Cited by 26 publications

References 44 publications

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Akt Kinase Mediates the Prosurvival Effect of Smoking Compounds in Pancreatic Ductal Cells

Bosentan inhibits cigarette smoke-induced endothelin receptor expression in pulmonary arteries

The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in southern and eastern chinese populations

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Cigarette smoke extract regulates cytosolic phospholipase A₂ expression via NADPH oxidase/MAPKs/AP‐1 and p300 in human tracheal smooth muscle cells