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Biochanin A protects against PM2.5-induced acute pulmonary cell injury by interacting with the target protein MEK5

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Abstract

Epidemiological studies have shown that exposure to ambient fine particulate matter (PM2.5) is associated with an increased risk for cardiopulmonary diseases. The MEK5/ERK5 and NF-κB signaling pathways are closely related to the regulation of acute pulmonary cell injury (APCI) and may play an important role in the underlying pathophysiological mechanisms. Related studies have shown that Biochanin A (BCA) effectively interferes with APCI, but the underlying mechanism through which this occurs is not fully understood. Previously, based on proteomic and bioinformatic research, we found the indispensable role of MEK5 in mediating remission effects of BCA against PM2.5-induced lung toxicity. Therefore, using A549 adenocarcinoma human alveolar basal epithelial cells (A549 cells), we combined western blot and qRT-PCR to study the protective signaling pathways induced by BCA, indicating that MEK5/ERK5 and NF-κB are both involved in mediating APCI in response to PM2.5, and MEK5/ERK5 positively activated NF-κB and its downstream cellular regulatory factors. BCA significantly suppressed PM2.5-induced upregulation of MEK5/ERK5 expression and phosphorylation and activation of NF-κB. Furthermore, due to the specificity of the MEK5/ERK5 protein structure, the binding sites and binding patterns of BCA and MEK5 were analyzed using molecular docking correlation techniques, which showed that there are stable hydrogen bonds between BCA and the PB1 domain of MEK5 as well as its kinase domain. BCA forms a stable complex with MEK5, which has potential effects on MEKK2/3-MEK5–ERK5 ternary interactions, p62/αPKC-mediated NF-κB regulation, and inhibition of MEK5 target protein phosphorylation. Therefore, our study suggests that MEK5 is an important regulator of intracellular signaling of APCI in response to PM2.5 exposure. BCA may exert anti-APCI activity by targeting MEK5 to inhibit activation of the MEK5/ERK5/NF-κB signaling pathway.

Graphical abstract: Biochanin A protects against PM2.5-induced acute pulmonary cell injury by interacting with the target protein MEK5

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Publication details

The article was received on 27 Jun 2019, accepted on 28 Sep 2019 and first published on 30 Sep 2019


Article type: Paper
DOI: 10.1039/C9FO01382B
Food Funct., 2019, Advance Article

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    Biochanin A protects against PM2.5-induced acute pulmonary cell injury by interacting with the target protein MEK5

    Z. Xue, J. Wang, W. Yu, D. Li, Y. Zhang, F. Wan and X. Kou, Food Funct., 2019, Advance Article , DOI: 10.1039/C9FO01382B

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