Inhibitory Activities of Ononin on Particulate Matter-induced Oxidative Stress
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING(2021)
Abstract
Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of less than 2.5 µm (PM 2.5 ) is associated with increased risk of respiratory injury, hospitalization, and respiratory death. The mechanism underlying the correlation between PM 2.5 exposure and adverse health effects has not been fully elucidated, but oxidative stress due to PM 2.5 appears to be an important molecular mechanism in PM 2.5 -mediated toxicity. The aim of this study was to determine the effects of ononin, a major isoflavone, on PM 2.5 -induced oxidative stress, and the mechanisms underlying these effects. Human pulmonary artery endothelial cells (HPAECs) were treated with PM 2.5 and then ononin. Exposure to PM 2.5 decreased cell viability in HPAECs in a time- and dose-dependent manner, possibly due to increased release of extracellular lactate dehydrogenase and generation of intracellular reactive oxygen species. PM 2.5 -induced oxidative damage was observed to occur via alterations to superoxide dismutase and catalase activities. Serum- and glucocorticoid-inducible kinase 1 (SGK1), a crucial cell survival factor, was downregulated by PM 2.5 . However, ononin treatment increased cell viability, decreased oxidative stress, and recovered the expression of SGK1 cell survival genes. Additionally, ononin increased the phosphorylation of mammalian target of rapamycin (mTOR) and dramatically suppressed the PM 2.5 -induced expression of toll-like receptor 4, MyD88, and the autophagy-related proteins LC3 II and Beclin 1. These findings indicate that ononin exhibits pulmonary protective effects against PM 2.5 -induced lung injury via inhibition of oxidative stress and mTOR-dependent autophagy pathways and is thus a potential therapeutic agent for PM 2.5 -induced lung injury.
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Key words
ononin, particulate matter, lung injury, mTOR-autophagy
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