| First Author | Wang H | Year | 2018 |
| Journal | Free Radic Biol Med | Volume | 121 |
| Pages | 202-214 | PubMed ID | 29753072 |
| Mgi Jnum | J:295006 | Mgi Id | MGI:6459304 |
| Doi | 10.1016/j.freeradbiomed.2018.05.008 | Citation | Wang H, et al. (2018) AMPKalpha2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction. Free Radic Biol Med 121:202-214 |
| abstractText | Previous studies have demonstrated that long-term exposure to fine particulate matter (PM2.5) 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 PM2.5 has not been investigated. In this study, we exposed wild-type (WT) and AMPKalpha2(-/-) mice to either airborne PM2.5 (mean daily concentration ~64microg/m(3)) or filtered air for 6 months through a whole-body exposure system. After exposure, AMPKalpha2(-/-) mice developed severe lung injury and left ventricular dysfunction. In the PM2.5-exposed lungs and hearts, loss of AMPKalpha2 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 PM2.5-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-kappaB 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 PM2.5 exposure. Our findings suggest that strategies to increase AMPK activity may provide a novel approach to attenuate air pollution associated disease. |
