Protein Misfolding and Endoplasmic Reticulum Stress in Chronic Lung Disease

Naiel, Safaa; Tat, Victor; Padwal, Manreet; Vierhout, Megan; Mekhael, Olivia; Yousof, Tamana; Ayoub, Anmar; Abed, Soumeya; Dvorkin‐Gheva, Anna; Ask, Kjetil

doi:10.1016/j.chest.2019.11.009

Cited by 26 publications

(18 citation statements)

References 110 publications

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“…In this disease, NPC2 gene mutations hinder the binding of unesterified cholesterol and the transportation of cholesterol to phospholipid vesicles, resulting in the change of composition of surfactant and the accumulation of enlarged lamellar bodies that are involved in inflammation and fibrosis of the lung parenchyma ( Cheruku et al, 2006 ; Roszell et al, 2012 ). Similarly, in case of familial idiopathic pulmonary fibrosis (IPF), accumulation of mutant pulmonary SP-C causes ER stress and endothelial dysfunction via increased endothelin-1, decreased NO, and endothelial cell apoptosis that augment lung fibrosis ( Naiel et al, 2019 ; Garcia, 2018 ). Furthermore, a human BAL fluid analysis showed that surfactant dysfunctions are typical features of IPF ( Günther et al, 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Park

Seong

Kang

et al. 2020

Toxicology and Applied Pharmacology

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Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.

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Section: Discussionmentioning

confidence: 99%

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Park

Seong

Kang

et al. 2020

Toxicology and Applied Pharmacology

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“…The increased degradation of misfolded proteins relieves the pressure on the ER and promotes cell survival ( 16 , 17 ). Previous studies have demonstrated that ERS serves an important role in lung diseases, including COPD, pulmonary fibrosis, acute lung injury and lung cancer ( 10 – 13 ). GPR78 is significantly upregulated by ERS only and is extensively used as a marker of ERS ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

“…The two main apoptosis pathways are the death receptor pathway and the mitochondrial pathway ( 8 , 9 ). Previous studies have demonstrated that endoplasmic reticulum stress (ERS)-related apoptosis is a noncanonical apoptosis pathway involved in several lung diseases, including chronic obstructive pulmonary disease (COPD), interstitial lung disease and lung cancer ( 10 – 13 ). The ERS-mediated apoptosis pathway has been investigated; however, only a few studies have assessed its role in BPD ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1α pathway in rats with bronchopulmonary dysplasia

Tong

Liu

et al. 2020

Mol Med Rep

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“…Recent studies demonstrated a role for ER stress in fibrosis in multiple organs, including the lungs [1,7]. For example, recent reports highlight the importance of ER stress and UPR in chronic obstructive pulmonary disease (COPD) [8][9][10], and the relation between ER stress and familial idiopathic pulmonary fibrosis (IPF) [7,11]. This review will focus on our current understanding of the role of ER stress and UPR in COPD and IPF.…”

Section: Introductionmentioning

confidence: 99%

The ER Stress/UPR Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

Aghaei

Dastghaib

Aftabi

et al. 2020

Life

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Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered as potential therapies. This review focuses on the impact of both external and internal stressors on the ER in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) and discusses the role of the UPR signaling pathway activation in the control of cellular damage and specifically highlights the potential involvement of non-coding RNAs in COPD. Summaries of pathogenic mechanisms associated with the ER stress/UPR axis contributing to IPF and COPD, and promising pharmacological intervention strategies, are also presented.

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Protein Misfolding and Endoplasmic Reticulum Stress in Chronic Lung Disease

Cited by 26 publications

References 110 publications

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1α pathway in rats with bronchopulmonary dysplasia

The ER Stress/UPR Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

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Protein Misfolding and Endoplasmic Reticulum Stress in Chronic Lung Disease

Cited by 26 publications

References 110 publications

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1&alpha; pathway in rats with bronchopulmonary dysplasia

The ER Stress/UPR Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis

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Hyperoxia induces endoplasmic reticulum stress‑associated apoptosis via the IRE1α pathway in rats with bronchopulmonary dysplasia