Dysfunctional Rhbdf2 of proopiomelanocortin mitigates ambient particulate matter exposure-induced neurological injury and neuron loss by antagonizing oxidative stress and inflammatory reaction.

Min-Xuan Xu, Xian-Ling Dai, Qin Kuang, Lian-Cai Zhu, Lin-Feng Hu, De-Shuai Lou, Qiang Li, Jing Feng, Ye-Kuan Wu, Chen-Xu Ge, Bo-Chu Wang, Jun Tan

Journal of hazardous materials 2020 Dec 05

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Ambient particulate matter (PM2.5)-induced metabolic syndromes is a critical contributor to the pathological processes of neurological diseases, but the underlying molecular mechanisms remain poorly understood. The rhomboid 5 homolog 2 (Rhbdf2), an essential regulator in the production of TNF-α, has recently been confirmed to exhibit a key role in regulating inﬂammation-associated diseases. Thus, we examined whether Rhbdf2 contributes to hypothalamic inflammation via NF-κB associated inflammation activation in long-term PM2.5-exposed mice. Specifically, proopiomelanocortin-specific Rhbdf2 deficiency (Rhbdf2Pomc) and corresponding littermates control mice were used for the current study. After 24 weeks of PM2.5 inhalation, systemic-metabolism disorder was confirmed in WT mice in terms of impaired glucose tolerance, increased insulin resistance, and high blood pressure. Markedly, PM2.5-treated Rhbdf2Pomc mice displayed a significantly opposite trend in these parameters compared with those of the controls group. We next confirmed hypothalamic injury accompanied by abnormal POMC neurons loss, as indicated by increased inflammatory cytokines, chemokines, and oxidative-stress levels and decreased antioxidant activity. These results were further supported by blood routine examination. In summary, our findings suggest that Rhbdf2 plays an important role in exacerbating PM2.5-stimulated POMC neurons loss associated hypothalamic injury, thus providing a possible target for blocking pathological development of air pollution-associated diseases. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Min-Xuan Xu, Xian-Ling Dai, Qin Kuang, Lian-Cai Zhu, Lin-Feng Hu, De-Shuai Lou, Qiang Li, Jing Feng, Ye-Kuan Wu, Chen-Xu Ge, Bo-Chu Wang, Jun Tan. Dysfunctional Rhbdf2 of proopiomelanocortin mitigates ambient particulate matter exposure-induced neurological injury and neuron loss by antagonizing oxidative stress and inflammatory reaction. Journal of hazardous materials. 2020 Dec 05;400:123158