Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1-Reference-Cited by-全球学者库

Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1

Published:2023-01-01 Issue:1 Volume:18 Page:
ISSN:2391-5463
Container-title:Open Medicine
language:en
Short-container-title:

Author:

You Yanjing¹,Wang Huijuan²,Wang Qing³,Yu Zongyang¹,Zhao Zhongquan¹,Zhuang Liying²,Zeng Shengyuan²,Zheng Jinyang²,Wen Wen⁴

Affiliation:

1. Department of Respiratory and Critical Care Medicine, Fuzhou General Hospital of Fujian Medical University, Dongfang Hospital of Xiamen University, 900TH Hospital of Joint Logistics Support Force, PLA , Fuzhou 350025 , Fujian , P.R. China

2. Graduate College of Fujian Medical University , Fuzhou 350025 , China

3. Department of Respiratory and Critical Care Medicine, The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine , Fuzhou 350108, Fujian , China

4. Department of Respiratory and Critical Care Medicine, Fuzhou General Hospital of Fujian Medical University, Dongfang Hospital of Xiamen University, 900TH Hospital of Joint Logistics Support Force, PLA , No. 156, Xi’erhuan North Road, Gulou District, Fuzhou 350025 , Fujian , P.R. China

Abstract

Abstract Chronic obstructive pulmonary disease (COPD) is commonly caused by smoking. FUN14 domain-containing protein 1 (FUNDC1) plays a fundamental role in mitochondrial autophagy and apoptosis in cigarette smoke extract (CSE)-treated BEAS-2B cells. The present study investigated the mechanism of action of FUNDC1 in mitochondrial dysfunction and apoptosis in CSE-treated BEAS-2B cells. The interaction between ubiquitin-specific peptidase 19 (USP19) and FUNDC1 was analyzed using co-immunoprecipitation. Effects of USP19 knockdown and/or FUNDC1 overexpression on the survival, apoptosis, mitochondrial membrane potential, and oxygen consumption rate (OCR) of BEAS-2B cells treated with 15% CSE were determined. In BEAS-2B cells, CSE inhibited cell survival, promoted apoptosis, increased the expression of USP19 and FUNDC1, increased the ratio of LC3 II to LC3 I (LC3 II/I), and decreased mitochondrial membrane potential and TOM20 levels. In CSE-treated BEAS-2B cells, USP19 knockdown reduced FUNDC1 and LC3 II/I, increased the levels of TOM20, improved cell survival, mitochondrial membrane potential, and OCR, and inhibited apoptosis. USP19 deubiquitinates FUNDC1. FUNDC1 overexpression inhibited the effect of USP19 knockdown in CSE-treated BEAS-2B cells. Overall, decreasing USP19 expression alleviates CSE-induced mitochondrial dysfunction in BEAS-2B cells by downregulating FUNDC1, providing novel insights into the molecular mechanism of FUNDC1 regulation in COPD.

Publisher

Walter de Gruyter GmbH

Subject

General Medicine

Link

https://www.degruyter.com/document/doi/10.1515/med-2023-0798/pdf

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