Nur77 promotes cigarette smoke‑induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1

Qin,Huiping; Gao,Feng; Wang,Yanni; Huang,Bin; Peng,Ling; Mo,Biwen; Wang,Changming

doi:10.3892/ijmm.2019.4184

Nur77 promotes cigarette smoke‑induced autophagic cell death by increasing the dissociation of Bcl2 from Beclin-1

Authors:
- Huiping Qin
- Feng Gao
- Yanni Wang
- Bin Huang
- Ling Peng
- Biwen Mo
- Changming Wang
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Affiliations: Department of Respiratory Medicine (Department of Respiratory and Critical Care Medicine), Key Site of The National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Respiratory Medicine, The Fifth Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541002, P.R. China, Department of Respiratory Medicine, Guilin Medical University, Guilin, Guangxi 541001, P.R. China
Published online on: May 8, 2019 https://doi.org/10.3892/ijmm.2019.4184
Pages: 25-36
Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible airflow limitation and persistent alveolar destruction, and autophagy is involved in the pathogenesis of cigarette smoke (CS)‑induced COPD. Nuclear receptor 77 (Nur77) participates in a number of biological processes, including apoptosis, autophagy and in disease pathogenesis; however, the role of Nur77 in COPD remains unknown. Thus, in this study, we aimed to elucidate the role of Nur77 in COPD. We report that CS promotes Nur77 expression and nuclear export in vivo and in vitro, which increases cigarette smoke extract (CSE)‑induced autophagy. In addition, we found that lung tissues, human bronchial epithelial (HBE) cells and A549 cells exposed to CS or CSE expressed lower levels of LC3 and Beclin‑1 and contained fewer autophagosomes following Nur77 knockdown with siRNA‑Nur77. Moreover, a co‑immunoprecipitation assay demonstrated that CSE promoted autophagy, partly by accelerating the interaction between Nur77 and Bcl2, in turn leading to the increased dissociation of Bcl2 from Beclin‑1; by contrast, leptomycin B (LMB) suppressed the dissociation of Bcl2 from Beclin‑1. Taken together, the findings of this study demonstrate that Nur77 is involved in the CSE‑induced autophagic death of lung cells, and that this process is partially dependent on the increased interaction between Nur77 and Bcl2, and on the dissociation of Bcl2 from Beclin‑1. This study illustrates the role of Nur77 in bronchial and alveolar destruction following exposure to CS.

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