High-Dose Paraquat Induces Human Bronchial 16HBE Cell Death and Aggravates Acute Lung Intoxication in Mice by Regulating Keap1/p65/Nrf2 Signal Pathway

Yao, Jiexiong; Zhang, Jihua; Tai, Wenlin; Deng, Shuhao; Li, Ting; Wu, Wenjuan; Lin, Ping; Du, F.; Wen, Lei; Zhang, Tao; Dong, Zhaoxing

doi:10.1007/s10753-018-00956-1

Cited by 19 publications

(8 citation statements)

References 34 publications

(48 reference statements)

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“…Ferroptosis is a newly characterized iron-dependent form of non-apoptotic regulated cell death triggered by lipid reactive oxygen species (ROS). Interestingly, several studies found that ROS levels were upregulated in the process of FMT induced by TGF-β1 [15,16], which was triggered by inflammatory cytokine secretion in PF [17][18][19]. Moreover, previous studies confirmed that iron overload could lead to PF, which is related to the increase in lipid peroxidation and the decrease in glutathione peroxidase 4 (GPX4) activity in lung tissues [20].…”

Section: Introductionmentioning

confidence: 98%

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Yang

Tai

et al. 2020

Aging

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Pulmonary fibrosis (PF) is a lethal fibrotic lung disease. The role of lncRNAs in multiple diseases has been confirmed, but the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in the progression of PF need to be elucidated further. Here, we found that lncRNA ZFAS1 was upregulated in bleomycin (BLM)-induced PF rats lung tissues and transforming growth factor-β1 (TGF-β1)-treated HFL1 cells, and positively correlated with the expression of solute carrier family 38 member 1 (SLC38A1), which is an important regulator of lipid peroxidation. Moreover, knockdown of lncRNA ZFAS1 significantly alleviated TGF-β1-induced fibroblast activation, inflammation and lipid peroxidation. In vivo experiments showed that inhibition of lncRNA ZFAS1 abolished BLM-induced lipid peroxidation and PF development. Mechanistically, silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. Collectively, our studies demonstrated the role of the lncRNA ZFAS1/miR-150-5p/SLC38A1 axis in the progression of PF, and may provide a new biomarker for the treatment of PF patients.

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Section: Introductionmentioning

confidence: 98%

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Yang

Tai

et al. 2020

Aging

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140

108

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“…PQ was reported to drive the apoptosis of various types of somatic cells both in vivo and in vitro [39,40,41]. In the process, dysfunction of mitochondria and induction of ROS were suggested to be critically involved [42].…”

Section: Discussionmentioning

confidence: 99%

Paraquat Preferentially Induces Apoptosis of Late Stage Effector Lymphocyte and Impairs Memory Immune Response in Mice

Shao

Zhao

Zhu

et al. 2019

IJERPH

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Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.

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“…In humans, PRQ poisoning, regardless of the route of administration, leads to multi-organ failure, pulmonary fibrosis causing respiratory failure and death ( Elenga et al, 2018 ). On human bronchial epithelial cells (16HBE) and in mice, it has been shown that a high dose of PRQ inhibits autophagy, cell proliferation, and promotes lung fibrosis by regulating the Keap1/P65/Nrf2 pathways ( Yao et al, 2019 ).…”

Section: Nrf2 and Diseasementioning

confidence: 99%

Role of Nrf2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches – Pulmonary Disease/Asthma

2021

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major transcription factor involved in redox homeostasis and in the response induced by oxidative injury. Nrf2 is present in an inactive state in the cytoplasm of cells. Its activation by internal or external stimuli, such as infections or pollution, leads to the transcription of more than 500 elements through its binding to the antioxidant response element. The lungs are particularly susceptible to factors that generate oxidative stress such as infections, allergens and hyperoxia. Nrf2 has a crucial protective role against these ROS. Oxidative stress and subsequent activation of Nrf2 have been demonstrated in many human respiratory diseases affecting the airways, including asthma and chronic obstructive pulmonary disease (COPD), or the pulmonary parenchyma such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Several compounds, both naturally occurring and synthetic, have been identified as Nrf2 inducers and enhance the activation of Nrf2 and expression of Nrf2-dependent genes. These inducers have proven particularly effective at reducing the severity of the oxidative stress-driven lung injury in various animal models. In humans, these compounds offer promise as potential therapeutic strategies for the management of respiratory pathologies associated with oxidative stress but there is thus far little evidence of efficacy through human trials. The purpose of this review is to summarize the involvement of Nrf2 and its inducers in ARDS, COPD, asthma and lung fibrosis in both human and in experimental models.

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High-Dose Paraquat Induces Human Bronchial 16HBE Cell Death and Aggravates Acute Lung Intoxication in Mice by Regulating Keap1/p65/Nrf2 Signal Pathway

Cited by 19 publications

References 34 publications

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150-5p/SLC38A1 axis

Paraquat Preferentially Induces Apoptosis of Late Stage Effector Lymphocyte and Impairs Memory Immune Response in Mice

Role of Nrf2 in Disease: Novel Molecular Mechanisms and Therapeutic Approaches – Pulmonary Disease/Asthma

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