Exposure to ultrafine particulate matter induces NF-κβ mediated epigenetic modifications
2019
Bhargava, Arpit | Shukla, Anushi | Bunkar, Neha | Shandilya, Ruchita | Lodhi, Lalit | Kumari, Roshani | Gupta, Pushpendra Kumar | Rahman, Akhlaqur | Chaudhury, Koel | Tiwari, Rajnarayan | Goryacheva, Irina Yu. | Mishra, Pradyumna Kumar
Exposure to ultrafine particulate matter (PM0.1) is positively associated with the etiology of different acute and chronic disorders; however, the in-depth biological imprints that link these submicron particles with the disturbances in the epigenomic machinery are not well defined. Earlier, we showed that exposure to these particles causes significant disturbances in the mitochondrial machinery and triggers PI-3-kinase mediated DNA damage responses. In the present study, we aimed to further understand the epigenomic insights of the ultrafine PM exposure. The higher levels of intracellular reactive oxygen species and depleted Nrf-2 in ultrafine PM exposed cells reconfirmed its potential to induce oxidative stress. Importantly, the observed increase in the levels of NF-κβ and associated cytokines among exposed cells suggested the activation of NF-κβ mediated inflammatory loop which potentially serves as a platform for initiating epigenetic insinuations. This fact was strongly supported by the altered miRNA expression profile of the ultrafine PM exposed cells. These NF-κβ induced miRNA alterations were also found to be associated with other epigenetic targets as the exposed cells showed higher expression levels of DNA methyltransferases which positively corresponded with the global changes in DNA methylation levels. Upon further analysis, significant alterations in histone code were also reported in ultrafine PM exposed cells. Conclusively our results suggested that NF-κβ acts as an inflammatory switch that possesses the potential to induce genome-wide epigenetic modification upon ultrafine PM exposure.
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