AMPKα2 deficiency exacerbates long-term PM 2.5 exposure-induced lung injury and cardiac dysfunction

Hongyun Wang, Xiyue Shen, Guoxiong Tian, Xili Shi, Wei Huang, Yongguang Wu, Lei Sun, Can Peng, Shasha Liu, Ying Huang, Xiaoyu Chen, Fang Zhang, Yingjie Chen, Wenjun Ding, Zhongbing Lu

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18 Scopus citations

Abstract

Previous studies have demonstrated that long-term exposure to fine particulate matter (PM 2.5 ) increases the risk of respiratory and cardiovascular diseases. As a metabolic sensor, AMP-activated protein kinase (AMPK) is a promising target for cardiovascular disease. However, the impact of AMPK on the adverse health effects of PM 2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKα2 -/- mice to either airborne PM 2.5 (mean daily concentration ~64 µg/m 3 ) or filtered air for 6 months through a whole-body exposure system. After exposure, AMPKα2 -/- mice developed severe lung injury and left ventricular dysfunction. In the PM 2.5 -exposed lungs and hearts, loss of AMPKα2 resulted in higher levels of fibrotic genes, more collagen deposition, lower levels of peroxiredoxin 5 (Prdx5), and greater induction of oxidative stress and inflammation than observed in the lungs and hearts of WT mice. In PM 2.5 -exposed BEAS-2B and H9C2 cells, inhibition of AMPK activity significantly decreased cell viability and Prdx5 expression, and increased the intracellular ROS and p-NF-κB levels. Collectively, our results provide the first direct evidence that AMPK has a marked protective effect on the adverse health effects induced by long-term PM 2.5 exposure. Our findings suggest that strategies to increase AMPK activity may provide a novel approach to attenuate air pollution associated disease.

Original languageEnglish (US)
Pages (from-to)202-214
Number of pages13
JournalFree Radical Biology and Medicine
Volume121
DOIs
StatePublished - Jun 2018

Keywords

  • AMPK
  • Heart failure
  • Lung injury
  • PM
  • Prdx5

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    Wang, H., Shen, X., Tian, G., Shi, X., Huang, W., Wu, Y., Sun, L., Peng, C., Liu, S., Huang, Y., Chen, X., Zhang, F., Chen, Y., Ding, W., & Lu, Z. (2018). AMPKα2 deficiency exacerbates long-term PM 2.5 exposure-induced lung injury and cardiac dysfunction Free Radical Biology and Medicine, 121, 202-214. https://doi.org/10.1016/j.freeradbiomed.2018.05.008