The Impact of Autophagy on the Cigarette Smoke Extract-Induced Apoptosis of Bronchial Epithelial Cells

Lee, Chang‐Hoon; Lee, Kyoung-Hee; Jang, An-Hee; Yoo, Chul‐Gyu

doi:10.4046/trd.2017.80.1.83

Cited by 21 publications

(18 citation statements)

References 22 publications

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“…Previous studies have revealed that CSE exposure can induce apoptosis, trigger ERS, UPR, and autophagy, and eventually results in the apoptosis of pulmonary cells under certain circumstances (30)(31)(32). A recent study also showed that CSE induces apoptosis, macroautophagy, and chaperone-mediated autophagy of bronchial epithelial cells (33). In line with this, our results showed that CSE treatment induced apoptosis, autophagy, and expression of ERS-related proteins in HBE cells.…”

Section: Discussionsupporting

confidence: 90%

Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract

Chen

Zhou

et al. 2018

IUBMB Life

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Endoplasmic reticulum stress (ERS)‐induced apoptosis of airway epithelial cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Furthermore, autophagy is closely related to ERS under apoptosis. Here, this study aimed to investigate the role of the reciprocal interaction between autophagy and ERS in the cigarette smoke extract (CSE)‐induced apoptosis of human bronchial epithelial (HBE) cells. Cell apoptosis was detected by flow cytometry analysis. Protein expression was examined by Western blot. The mRNA expression was detected using real‐time quantitative reverse transcription PCR (qRT‐PCR). The results showed that CSE treatment induced apoptosis, autophagy, and expression of ERS‐related proteins in HBE cells. Furthermore, autophagy inhibition by 3‐MA significantly decreased protein expression of GRP78, p‐PERK, and p‐eIF2α and increased CHOP, ATF4, and caspase‐4, whereas ERS inhibition by 4‐PBA led to autophagy suppression. Moreover, the CSE‐induced autophagy was diminished by knockdown of GRP78, PERK, or eIF2α but enhanced by knockdown of ATF4 or CHOP; however, the CSE‐induced HBE apoptosis was enhanced by knockdown of GRP78, PERK, or eIF2α but was attenuated by knockdown of ATF4 or CHOP. Additionally, both sodium hydrosulfide (NaHS) and melatonin attenuated the CSE‐induced apoptosis, enhanced the CSE‐induced autophagy, increased GRP78, p‐PERK, and p‐eIF2α, and decreased CHOP, ATF4, and caspase‐4, via SIRT1/ORP150 pathway. Collectively, this study provided evidence about the role of the reciprocal interaction between autophagy and ERS in CSE‐induced apoptosis of HBE cells. © 2018 IUBMB Life, 71(1):66–80, 2019

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Section: Discussionsupporting

confidence: 90%

Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract

Chen

Zhou

et al. 2018

IUBMB Life

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“…Previous studies have shown that the decrease in cell viability due to CS exposure is related to apoptosis and autophagy . So, we investigated the activation of apoptosis and autophagy.…”

Section: Discussionmentioning

confidence: 97%

Cigarette smoke extract and isoprene resulted in the induction of apoptosis and autophagy in human placenta choriocarcinoma JEG‐3 cells

Lee

Choi

2017

Environmental Toxicology

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In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment. Moreover, 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay revealed increased ROS production. Upon 3-(4-5-dimethylthiazol-2-yl)-2.5-dyhphenyltetrazolium bromide (MTT) assay, isoprene (IP), one of ingredients of CS, deceased JEG-3 cell viability (10 to 10 M). After based on the MTT assay, two IP concentrations of 10 and 10 M were selected and the protein expressions of cyclin D1, cyclin E1, p21, and p27 decreased in response to IP. Furthermore, IP showed the greatest increase in autophagy at 24 hours and further induction of cell death at 72 hours upon monodansylacadaverine and TUNEL assay. Western blot analysis confirmed the increase in autophagy markers, LC3β and p62, as well as the increase or decrease of apoptosis markers p53, Bax, CHOP, and Bcl-2 in response to its treatments. In addition to confirming increases in ROS through DCFH-DA, we also confirmed the expression of Nrf2, an antioxidant marker, and the expression of Kelch-like ECH-associated protein 1 (KEAP1), which specifically degrades Nrf2, by Western blot. Taken together, these results indicate that CS and IP may inhibit the development of placenta via activation of ROS by inducing apoptosis and autophagy by affecting the expression of KEAP1, which regulates Nrf2 expression.

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“…However, excessive ERS can lead to programmed cell death through an ERS-associated apoptosis pathway and activation of Caspase 12 in rodents (Caspase 4 in human) (Kaufman, 2002; Ron, 2002; Ron and Walter, 2007). Several studies have reported CSE-induced apoptosis in vitro , especially ERS associated cell apoptosis (Lee et al, 2017a; Lee et al, 2017b; Jiao et al, 2017; Song et al, 2017; Iu et al, 2017). This process involves UPR signaling pathways activation, induced via ER transmembrane molecules, including PERK, IRE1 and ATF6, and sequence different signaling pathways, final activating ERS-associated apoptosis (Tokunaga et al, 2010; Gan et al, 2011; Tagawa et al, 2011; Yuan et al, 2012; Kitaguchi et al, 2012; Kelsen, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Nearly 90% of COPD cases are caused by cigarette smoke (Martinez and Han, 2012). Cigarette smoke (CS) induces an imbalance of cell proliferation and apoptosis, which is thought to be critical in the pathogenesis of COPD, and determine disease phenotype (Haw et al, 2016; Bodas et al, 2016; Lee et al, 2017a; Lee et al, 2017b). The three classical apoptotic pathways: endoplasmic reticulum stress (ERS), intrinsic, and extrinsic apoptotic pathways all have been implicated in the pathogenesis of COPD (Wu et al, 2015; Fujita et al, 2016; Yuan et al, 2017; Lin et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Ursolic Acid Protected Lung of Rats From Damage Induced by Cigarette Smoke Extract

Hou

Han

et al. 2019

Front. Pharmacol.

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Background: We found previously that ursolic acid (UA) administration could alleviate cigarette smoke-induced emphysema in rats partly through the unfolded protein response (UPR) PERK-CHOP and Nrf2 pathways, thus alleviating endoplasmic reticulum stress (ERS)-associated oxidative stress and cell apoptosis. We hypothesized that other UPR pathways may play similar roles in cigarette smoke extract (CSE)-induced emphysema. So, we sought to investigate the dynamic changes and effects of UPR and the downstream apoptotic pathways. Further, we investigated whether UA could alleviate CSE-induced emphysema and airway remodelling in rats, whether and when it exerts its effects through UPR pathways as well as Smads pathways. Methods: One hundred eight Sprague Dawley (SD) rats were randomly divided into three groups: Sham group, CSE group, and UA group, and each group was further divided into three subgroups, administered CSE (vehicle) for 2, 3, or 4 weeks; each subgroup had 12 rats. We examined pathological changes, analyzed the three UPR signaling pathways and subsequent ERS, intrinsic and extrinsic apoptotic pathway indicators, as well as activation of Smad2,3 molecules in rat lungs. Results: Exposure to CSE for 3 or 4 weeks could apparently induce emphysema and airway remodeling in rats, including gross and microscopic changes, alteration of mean alveolar number (MAN), mean linear intercept (MLI), and mean airway thickness in lung tissue sections. UA intervention could significantly alleviate CSE-induced emphysema and airway remodeling in rats. UA exerted its effects through ameliorating apoptosis by down regulating UPR signalling pathways and subsequent apoptosis pathways, as well as, downregulating p-Smad2 and p-Smad3 molecules. Conclusions: UA attenuated CSE-induced emphysema and airway remodeling, exerting its effects partly through regulation of three UPR pathways, amelioration downstream apoptotic pathways, and alleviating activation of Smad2 and Smad3.

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The Impact of Autophagy on the Cigarette Smoke Extract-Induced Apoptosis of Bronchial Epithelial Cells

Cited by 21 publications

References 22 publications

Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract

Role of reciprocal interaction between autophagy and endoplasmic reticulum stress in apoptosis of human bronchial epithelial cells induced by cigarette smoke extract

Cigarette smoke extract and isoprene resulted in the induction of apoptosis and autophagy in human placenta choriocarcinoma JEG‐3 cells

Ursolic Acid Protected Lung of Rats From Damage Induced by Cigarette Smoke Extract

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