Resveratrol exerts an anti-apoptotic effect on human bronchial epithelial cells undergoing cigarette smoke exposure

Zhang,Li; Guo,Xialing; Xie,Wang; Li,Yuping; Ma,Miao; Yuan,Ting; Luo,Bailing

doi:10.3892/mmr.2014.2925

Resveratrol exerts an anti-apoptotic effect on human bronchial epithelial cells undergoing cigarette smoke exposure

Authors:
- Li Zhang
- Xialing Guo
- Wang Xie
- Yuping Li
- Miao Ma
- Ting Yuan
- Bailing Luo
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Affiliations: Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Critical Emergency Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410007, P.R. China
Published online on: November 11, 2014 https://doi.org/10.3892/mmr.2014.2925
Pages: 1752-1758
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Cigarette smoke can cause endoplasmic reticulum stress and induce apoptosis, both of which are important pathogenic factors contributing to chronic obstructive pulmonary disease. The aim of the present study was to produce a cigarette smoke extract (CSE)‑induced apoptosis human bronchial epithelial cell (HBEpC) model, to investigate the protective effects of resveratrol (RES). The role of oxygen‑regulated protein 150 (ORP150) in the RES‑induced activation of Sirtuin 1 (SIRT1) was additionally studied. Cultured HBEpCs were initially treated with CSE to induce apoptosis, followed by an incubation either with or without RES. Numerous techniques were used to evaluate the outcomes of the present study, including cell counting kit‑8 assay, quantitative polymerase chain reaction, western blotting, Hoechst 33342 staining and AnnexinV‑PI flow cytometry apoptosis analyses, and gene knockdown. It was identified that 24 h 2% CSE incubation induced apoptosis in HBEpC, accompanied by an overexpression of the apoptosis molecular markers CCAAT‑enhancer‑binding protein homologous protein, caspase 4 and caspase 3. Pre‑treatment of the cells with RES markedly alleviated the severity of apoptosis, as confirmed by apoptosis analyses and the expression levels of the apoptosis molecular markers. SIRT1 was shown to be overexpressed following RES treatment. However, following the gene knockdown of ORP150, the anti‑apoptotic effects of RES were significantly attenuated. The results of the present study demonstrate that RES may have a protective effect against CSE‑induced apoptosis, and a molecular pathway involving SIRT1 and ORP150 may be associated with the anti‑apoptotic functions of RES in HBEpC.

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1	Pauwels RA and Rabe KF: Burden and clinical featuRES of chronic obstructive pulmonary disease (COPD). Lancet. 364:613–620. 2004. View Article : Google Scholar : PubMed/NCBI
2	Demedts IK, Demoor T, Bracke KR, Joos GF and Brusselle GG: Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema. RESpir RES. 7:532006. View Article : Google Scholar : PubMed/NCBI
3	Kuwano K: Epithelial cell apoptosis and lung remodeling. Cell Mol Immuno. 4:419–429. 2007.
4	Kelsen SG, Duan X, Ji R, Perez O, Liu C and Merali S: Cigarette smoke induces an unfolded protein RESponse in the human lung: a proteomic approach. Am J RESpir Cell Mol Biol. 38:541–550. 2008. View Article : Google Scholar
5	Kim I, Xu W and Reed JC: Cell death and endoplasmic reticulum stRESs: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 7:1013–1030. 2008. View Article : Google Scholar : PubMed/NCBI
6	Rahman I, Kinnula VL, Gorbunova V and Yao H: SIRT1 as a therapeutic target in inflammaging of the pulmonary disease. Prev Med. 54:S20–S28. 2012. View Article : Google Scholar :
7	Lagouge M, Argmann C, Gerhart-Hines Z, et al: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 127:1109–1122. 2006. View Article : Google Scholar : PubMed/NCBI
8	Wood JG, Rogina B, Lavu S, et al: Sirtuin activators mimic caloric REStriction and delay ageing in metazoans. Nature. 430:686–689. 2004. View Article : Google Scholar : PubMed/NCBI
9	Chen CJ, Yu W, Fu YC, Wang X, Li JL and Wang W: Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway. Biochem Biophys RES Commun. 378:389–393. 2009. View Article : Google Scholar
10	Csiszar A, Labinskyy N, Podlutsky A, et al: Vasoprotective effects of Resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stRESs and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol. 294:H2721–H2735. 2008. View Article : Google Scholar : PubMed/NCBI
11	Anekonda TS and Adamus G: Resveratrol prevents antibody-induced apoptotic death of retinal cells through upregulation of Sirt1 and Ku70. BMC RES Notes. 1:1222008. View Article : Google Scholar : PubMed/NCBI
12	Liu LQ, Fan ZQ, Tang YF and Ke ZJ: The Resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER-related caspase-12 activation and PDE activity in vitro. Alcohol Clin Exp RES. 38:683–693. 2014. View Article : Google Scholar
13	Yao H, Chung S, Hwang JW, et al: SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 122:2032–2045. 2012. View Article : Google Scholar : PubMed/NCBI
14	Rajendrasozhan S, Yang SR, Kinnula VL and Rahman I: SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am J Crit Care Med. 177:861–870. 2008. View Article : Google Scholar
15	Tagawa Y, Hiramatsu N, Kasai A, et al: Induction of apoptosis by cigarette smoke via ROS-dependent endoplasmic reticulum stRESs and CCAAT/enhancer-binding protein-homologous protein (CHOP). Free Radic Biol Med. 45:50–59. 2008. View Article : Google Scholar : PubMed/NCBI
16	Wu YB, Li HQ, Ren MS, Li WT, Lv XY and Wang L: CHOP/ORP150 ratio in endoplasmic reticulum stress: a new mechanism for diabetic peripheral neuropathy. Cell Physiol Biochem. 32:367–379. 2013. View Article : Google Scholar : PubMed/NCBI
17	Jung TW, Lee KT, Lee MW and Ka KH: SIRT1 attenuates palmitate-induced endoplasmic reticulum stRESs and insulin RESistance in HepG2 cells via induction of oxygen-regulated protein 150. Biochem Biophys RES Commun. 422:229–232. 2012. View Article : Google Scholar : PubMed/NCBI
18	Kusaczuk M and Cechowska-Pasko M: Molecular chaperone ORP150 in ER stRESs-related diseases. Curr Pharm Des. 19:2807–2818. 2013. View Article : Google Scholar : PubMed/NCBI
19	Wang Y, Wu Z, Li D, et al: Involvement of oxygen-regulated protein 150 in AMP-activated protein kinase-mediated alleviation of lipid-induced endoplasmic reticulum stRESs. J Biol Chem. 286:11119–11131. 2011. View Article : Google Scholar : PubMed/NCBI
20	Braber S, Koelink PJ, Henricks PA, et al: Cigarette smoke-induced lung emphysema in mice is associated with prolyl endopeptidase, an enzyme involved in collagen breakdown. Am J Physiol Lung Cell Mol Physiol. 300:L255–L265. 2011. View Article : Google Scholar :
21	Yuan T, Luo BL, Wei TH, Zhang L, He BM and Niu RC: Salubrinal protects against cigarette smoke extract-induced HBEpC apoptosis likely via regulating the activity of PERK-eIF2α signaling pathway. Arch Med RES. 43:522–529. 2012. View Article : Google Scholar : PubMed/NCBI
22	Xiong XL, Jia RH, Yang DP and Ding GH: Irbesartan attenuates contrast media-induced NRK-52E cells apoptosis. Pharmacol RES. 54:253–260. 2006. View Article : Google Scholar : PubMed/NCBI
23	Tagawa Y, Hiramatsu N, Kato H, et al: Induction of CCAAT/enhancer-binding protein-homologous protein by cigarette smoke through the superoxide anion-triggered PERK-eIF2α pathway. Toxicology. 287:105–112. 2011. View Article : Google Scholar : PubMed/NCBI
24	He B, Luo B, Chen Q and Zhang L: Cigarette smoke extract induces the expression of GRP78 in A549 cells via the p38/MAPK pathway. Mol Med Rep. 8:1683–1688. 2013.PubMed/NCBI
25	Hodge S, Hodge G, Holmes M and Reynolds PN: Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation. Eur Respir J. 25:447–454. 2005. View Article : Google Scholar : PubMed/NCBI
26	Tagawa Y, Hiramatsu N, Kasai A, Hayakawa K, Okamura M, Yao J and Kitamura M: Induction of apoptosis by cigarette smoke via ROS-dependent endoplasmic reticulum stress and CCAAT/enhancer-binding protein-homologous protein (CHOP). Free Radic Biol Med. 45:50–59. 2008. View Article : Google Scholar : PubMed/NCBI
27	Yao H, Chung S, Hwang JW, Rajendrasozhan S, Sundar IK, Dean DA, McBurney MW, Guarente L, Gu W, Rönty M, et al: SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest. 122:2032–2045. 2012. View Article : Google Scholar : PubMed/NCBI
28	Malhotra D, Thimmulappa R, Vij N, et al: Heightened endoplasmic reticulum stRESs in the lungs of patients with chronic obstructive pulmonary disease: the role of Nrf2-regulated proteasomal activity. Am J RESpir Crit Care Med. 180:1196–1207. 2009. View Article : Google Scholar : PubMed/NCBI
29	Tanel A, Pallepati P, Bettaieb A, Morin P and Averill-Bates DA: Acrolein activates cell survival and apoptotic death RESponses involving the endoplasmic reticulum in A549 lung cells. Biochim Biophys Acta. 1843.827–835. 2014.