Cigarette smoke extract stimulates bronchial epithelial cells to undergo a SUMOylation turnover

Haifeng Zhou,Lei Zhang,Yang Li,Qilin Yu,Cong-Yi Wang,Lei Guo,Jibao Cai,Qing Zhou,Shu Zhang,Ping Yang,Guorao Wu,Jia-Kun Su,Fei Xiong,Huilan Zhang,He Zhu

doi:10.1186/s12890-020-01300-w

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Although the detailed mechanisms of this disease remain elusive, there is feasible evidence that protein posttranslational modifications (PTMs) may play a role in its pathoetiology. We thus conducted studies to dissect the effect of cigarette smoke extracts (CSE) on the change of SUMOylated substrates in human bronchial epithelial cells (HBEs).MethodsSamples were collected in HBEs with or without 24 h of CSE insult and then subjected to Western-blot and LC-MS/MS analysis. Subsequently, bioinformatic tools were used to analyze the data. The effect of SUMOylation on cytochrome P450 1A1 (CYP1A1) was evaluated by flow cytometry.ResultsIt was noted that CSE stimulated HBEs to undergo a SUMOylation turnover as evidenced by the changes of SUMOylated substrates and SUMOylation levels for a particular substrate. The SUMOylated proteins are relevant to the regulation of biological processes, molecular function and cellular components. Particularly, CSE stimulated a significant increase of SUMOylated CYP1A1, a critical enzyme involved in the induction of oxidative stress.ConclusionsOur data provide a protein SUMOylation profile for better understanding of the mechanisms underlying COPD and support that smoking induces oxidative stress in HBEs, which may predispose to the development of COPD in clinical settings.

Highlights

Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke
Our study revealed that cigarette smoke extracts (CSE) significantly enhanced cytochrome P450 1A1 (CYP1A1) SUMOylation, indicating that oxidative stress induced by smoking plays a critical role in human bronchial epithelial cells (HBEs) injury, which may contribute to the initiation and progression of COPD
CSE induces HBEs to undergo a SUMOylation turnover To demonstrate the effect of cigarette smoking on the changes of SUMOylated proteins in HBEs, we examined the expression of small ubiquitin-like modifier (SUMO) proteins and SUMOylation associated enzymes following CSE stimulation

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) characterized by the airway and lung inflammation, is a leading cause of morbidity and mortality worldwide, especially among smokers over 40 years of age and individuals exposed to biomass smoke. Chronic obstructive pulmonary disease (COPD), which affects more than 10% of population over 40 years of age, is a leading cause of hospital admissions and is currently the third leading cause of death worldwide [1]. Posttranslational modifications (PTMs) are a common and reversible regulatory modification that allows the cells being able to regulate the function of proteins in response to intra- and extracellular signals. SUMOylation, one of the evolutionarily conserved reversible PTMs, is featured by the covalent attachment of the small ubiquitin-like modifier (SUMO) to its substrate proteins. SUMOylation is employed by almost all eukaryotes to regulate many cellular processes such as gene expression, genome stability, DNA damage repair, RNA processing, cell cycle progression and quality control of newly synthesized proteins [8, 10]

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