Mitochondrial superoxide mediates PM2.5-induced cytotoxicity in human pulmonary lymphatic endothelial cells
| Autor: | Ye Cui, Guang Chen, Zeran Yang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Reactive oxygen species 010504 meteorology & atmospheric sciences Chemistry Health Toxicology and Mutagenesis government.form_of_government SOD2 General Medicine 010501 environmental sciences Lung injury Mitochondrion Toxicology complex mixtures 01 natural sciences Pollution Cell biology Lymphatic Endothelium Lymphatic system government Viability assay PI3K/AKT/mTOR pathway 0105 earth and related environmental sciences |
| Zdroj: | Environmental Pollution. 263:114423 |
| ISSN: | 0269-7491 |
| DOI: | 10.1016/j.envpol.2020.114423 |
| Popis: | Exposure to airborne fine particulate matter (PM2.5) is associated with a variety of respiratory health effects and contributes to premature mortality. Lymphatic vessels are instrumental in facilitating the transport of toxic materials away from the lung to maintain alveolar clearance and have been shown to play important roles in lung injury and repair. Despite intense research efforts in delineating the effects of PM2.5 on blood vascular endothelial cells, the impacts of PM2.5 on lymphatic endothelial cells (LECs), a specialized subset of endothelial cells that comprise lymphatic vessels, remain enigmatic. Here, we conducted MTT assay and show that treatment of human pulmonary LECs with PM2.5 suppresses cell viability in a time- and dose-dependent manner. We subsequently performed Annexin V/propidium iodide labeling and demonstrate that PM2.5 induces LECs apoptosis and necrosis. Furthermore, we found that manganese superoxide dismutase (SOD2) expression and mitochondrial SOD activity were profoundly reduced following PM2.5 exposure. Mechanistically, we provide compelling evidence that PM2.5 reduces SOD2 expression through activation of Akt pathway, which leads to a disruption of mitochondrial redox homeostasis characterized by increased accumulation of mitochondrial superoxide. Conversely, mitochondria-targeted SOD mimetic (MitoTEMPO) corrects the disturbed oxidative milieu in PM2.5-treated LECs. Additionally, MitoTEMPO ameliorates the deleterious impacts of PM2.5 on mitochondrial DNA integrity and preserves the viability of LECs. Taken together, these novel data support a critical role for mitochondrial superoxide in the pathogenesis of PM2.5-induced LECs injury and identity mitochondrial-targeted antioxidants as promising therapeutic options to treat environmental lung diseases. Our findings are limited to experimental studies with primary LECs, and future investigations in animal models are warranted to shed light on the precise pathophysiology of lymphatic system in response to PM exposure. |
| Databáze: | OpenAIRE |
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