The mitochondria-targeted antioxidant MitoQ attenuated PM2.5-induced vascular fibrosis via regulating mitophagy

Ning, Ruihong; Li, Yang; Du, Zhou; Li, Tianyu; Sun, Qinglin; Lin, Lisen; Xu, Qing; Duan, Junchao; Sun, Zhiwei

doi:10.1016/j.redox.2021.102113

Cited by 45 publications

(23 citation statements)

References 59 publications

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“…Previous studies showed that oxidative stress participated in regulating PM-induced inflammatory response, cell apoptosis, and even lung injury [ 33 , 34 ]. Ning et al found that the expression of antioxidant enzymes, superoxide dismutase 2 (SOD2), SOD3, and peroxiredoxin 4 (PRDX4) was decreased in PM-exposed lung tissues of mice [ 35 ]. Similar to these previous studies, we detected that PM exposure decreased MMP and further promoted ROS production in HBECs.…”

Section: Discussionmentioning

confidence: 99%

Edaravone Attenuated Particulate Matter-Induced Lung Inflammation by Inhibiting ROS-NF-κB Signaling Pathway

Zeng

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Particulate matter (PM) exposure is related to mitochondria dysfunction and airway inflammation. Antioxidant drug edaravone (EDA) is reported to improve the occurrence and development of oxidative stress-related diseases. At present, there is no data on whether EDA can alleviate lung inflammation caused by PM. Methods. The anti-inflammatory effects of EDA were investigated in urban PM-induced human bronchial epithelial cells (HBECs) and C57/BL6J mouse models. In vitro, its effects on the production of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were assessed by DCFH-DA staining, JC-1 assay, and real-time PCR, respectively. In vivo, the oxidant stress in lung tissues was assessed by dihydroethidium (DHE) staining and malondialdehyde (MDA) activity, and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were assessed by ELISA, respectively. Furthermore, the potential signaling pathways were studied by siRNA transfection and western blot. Results. PM increased the expression of inflammatory cytokines and protein, including IL-6, IL-1α, IL-1β, and COX-2, while these alternations were significantly alleviated following EDA treatment in a dose-dependent manner. EDA treatment also alleviated the inflammatory responses in lung tissues of PM-exposed mice. We further showed mitochondrial dysfunction in PM-exposed HBECs and mice, which were reversed by EDA treatment. Moreover, the phosphorylation of NF-κB p65 in PM-exposed HBECs and mice was weakened by EDA. Transfection with NF-κB p65 siRNA further inhibited PM-induced inflammation in HBECs. Conclusion. We demonstrated that EDA treatment had a protective role in PM-induced lung inflammation through maintaining mitochondrial balance and regulating the ROS-NF-κB p65 signaling pathway. This provided a new therapeutic method for PM-induced lung inflammation in the future.

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Section: Discussionmentioning

confidence: 99%

Edaravone Attenuated Particulate Matter-Induced Lung Inflammation by Inhibiting ROS-NF-κB Signaling Pathway

Zeng

Zhu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Mito-Q, a mitochondria-targeted antioxidant, can protect the vascular function and structure of C57 mice (150)(151)(152); and can inhibit the excessive production of mitochondrial ROS, increase the expression of superoxide dismutase 2 (SOD2), and restore the relative levels of mitochondrial membrane potential (MMP), oxygen consumption rate (OCR), and ATP. In addition, it indirectly regulate PINK1/Parkin mediated mitophagy and mitochondrial fusion/fission mechanisms (153). Collectively, these studies build a good reference for the study of targeted drugs for vascular injury associated with CHD.…”

Section: Pharmacological Intervention In Animalsmentioning

confidence: 91%

Role of Mitophagy in Coronary Heart Disease: Targeting the Mitochondrial Dysfunction and Inflammatory Regulation

Liu

2022

Front. Cardiovasc. Med.

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Coronary heart disease (CHD) is one of the main causes of death worldwide. In the past few decades, several in-depth research on the pathological mechanisms and effective treatment methods for CHD have been conducted. At present, the intervention of a variety of therapeutic drugs and treatment technologies have greatly reduced the burden on global public health. However, severe arrhythmia and myocardial fibrosis accompanying CHD in the later stages need to be addressed urgently. Mitochondria are important structural components for energy production and the main sites for aerobic respiration in cells. Mitochondria are involved in arrhythmia, myocardial fibrosis, and acute CHD and play a crucial role in regulating myocardial ischemia/hypoxia. Mitochondrial dysfunction or mitophagy disorders (including receptor-dependent mitophagy and receptor-independent mitophagy) play an important role in the pathogenesis of CHD, especially mitophagy. Mitophagy acts as a “mediator” in the inflammatory damage of cardiomyocytes or vascular endothelial cells and can clear mitochondria or organelles damaged by inflammation under normal conditions. We reviewed experimental advances providing evidence that mitochondrial homeostasis or mitochondrial quality control are important in the pathological mechanism of CHD. Further, we reviewed and summarized relevant regulatory drugs that target mitochondrial function and quality control.

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“…For this reason, the daily exposure of mice was 0.035208∗35 μ g/m 3 = 1.23228 μ g. Based on the body weight of mice 25 g and the extrapolation coefficient of species 100, the volume of intratracheal instillation was 1.23228 μ g/25 g∗100 = 4.93 μ g/g. Previous studies have demonstrated that PM 2.5 at 5 mg/kg can cause varying degrees of organ damage [ 38 , 39 ]. Therefore, a dose of 5 mg/kg was selected for animal modeling.…”

Section: Methodsmentioning

confidence: 99%

Melatonin Alleviates PM2.5-Induced Hepatic Steatosis and Metabolic-Associated Fatty Liver Disease in ApoE-/- Mice

Liang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Exposure to fine particulate matter (PM2.5) is associated with the risk of developing metabolic-associated fatty liver disease (MAFLD). Melatonin is the main secreted product of the pineal gland and has been reported to prevent hepatic lipid metabolism disorders. However, it remains uncertain whether melatonin could protect against PM2.5-induced MAFLD. Methods and Results. The purpose of our study was to investigate the mitigating effects of melatonin on hepatic fatty degeneration accelerated by PM2.5 in vivo and in vitro. Histopathological analysis and ultrastructural images showed that PM2.5 induced hepatic steatosis and lipid vacuolation in ApoE-/- mice, which could be effectively alleviated by melatonin administration. Increased ROS production and decreased expression of antioxidant enzymes were detected in the PM2.5-treated group, whereas melatonin showed recovery effects after PM2.5-induced oxidative damage in both the liver and L02 cells. Further investigation revealed that PM2.5 induced oxidative stress to activate PTP1B, which in turn had a positive feedback regulation effect on ROS release. When a PTP1B inhibitor or melatonin was administered, SP1/SREBP-1 signalling was effectively suppressed, while Nrf2/Keap1 signalling was activated in the PM2.5-treated groups. Conclusion. Our study is the first to show that melatonin alleviates the disturbance of PM2.5-triggered hepatic steatosis and liver damage by regulating the ROS-mediated PTP1B and Nrf2 signalling pathways in ApoE-/- mice. These results suggest that melatonin administration might be a prospective therapy for the prevention and treatment of MAFLD associated with air pollution.

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The mitochondria-targeted antioxidant MitoQ attenuated PM2.5-induced vascular fibrosis via regulating mitophagy

Cited by 45 publications

References 59 publications

Edaravone Attenuated Particulate Matter-Induced Lung Inflammation by Inhibiting ROS-NF-κB Signaling Pathway

Edaravone Attenuated Particulate Matter-Induced Lung Inflammation by Inhibiting ROS-NF-κB Signaling Pathway

Role of Mitophagy in Coronary Heart Disease: Targeting the Mitochondrial Dysfunction and Inflammatory Regulation

Melatonin Alleviates PM2.5-Induced Hepatic Steatosis and Metabolic-Associated Fatty Liver Disease in ApoE-/- Mice

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