Resveratrol reduces the apoptosis induced by cigarette smoke extract by upregulating MFN2.

Chao Song,Bailing Luo,Li Gong,Yi-Hsien Hsieh

doi:10.1371/journal.pone.0175009

Chao Song, Bailing Luo + Show 2 more

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https://doi.org/10.1371/journal.pone.0175009

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Abstract

PurposeThe aim of this study was to investigate the effect of resveratrol (RSV) on cigarette smoke extract (CSE)-induced cell apoptosis and mitochondrial dysfunction in vitro, as well as changes in the MFN2 expression level.MethodsCultured human bronchial epithelial (HBE) cells were initially treated with CSE to induce apoptosis, followed by incubation either with or without RSV. Numerous techniques were used to evaluate the outcomes of the present study, including a cell counting kit-8 assay, real-time quantitative polymerase chain reaction (real-time qPCR), western blotting, JC-1 fluorescence, Hoechst 33342 staining, Annexin V-PI flow cytometry apoptosis analyses, and siRNA technology.ResultsA 24 h incubation in 3.5% CSE induced apoptosis in HBE cells, and pretreatment of HBE cells with RSV (20 μM) significantly suppressed the CSE-induced apoptosis, prevented the CSE-induced decrease in MFN2 levels, suppressed BAX translocation to the mitochondria, and prevented mitochondrial membrane potential loss and cytochrome C release. However, following the transfection of MFN2 siRNA, the anti-apoptotic effects of RSV were significantly attenuated.ConclusionThe results of the present study demonstrated that RSV may protect bronchial epithelial cells from CS-induced apoptosis in vitro by preventing mitochondrial dysfunction, and MFN2 may be associated with the anti-apoptotic functions of RSV in HBE cells.

Highlights

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world[1], and smoking is one of the most important causes of the disease
The results of the present study demonstrated that RSV may protect bronchial epithelial cells from CS-induced apoptosis in vitro by preventing mitochondrial dysfunction, and mitofusin 2 (MFN2) may be associated with the anti-apoptotic functions of RSV in human bronchial epithelial (HBE) cells
Mitochondrial fission in mammals is mediated by dynamin-related protein 1 (Drp1), which interacts with four mitochondrial receptor proteins: fission 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics protein of 49 kDa (MID49) and MID51

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the world[1], and smoking is one of the most important causes of the disease. Recent studies from around the world have found that, under the stimulation of cigarette smoke extract (CSE), abnormal mitochondrial morphology, the increase of mitochondrial fragments, and the dysfunction of mitochondria in cells can be observed[3,4,5]. Mitochondrial fusion in mammals is mediated by the fusion proteins mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1). Severe stress can lead to mitochondrial fusion disorder; fusion is reduced, fission is increased, mitochondrial fragmentation is increased, the level of energy metabolism is decreased, ATP production capacity is decreased, the mitochondrial function is disordered, the self-repair capacity is decreased, and, all these disorders induce oxidative stress and cell apoptosis. MFN2, as an important member of the mitochondrial fusion protein family, plays a key role in the process of mitochondrial fusion. Studies have shown that MFN2 plays an important role in the occurrence and development of metabolic diseases, such as cardiovascular disease, cancer, and type 2 hereditary motor and sensory neuropathy (Charcot-Marie-Tooth, disease, CMT2)[8,9,10]

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