AMPKα2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction
AMPKα2 deficiency exacerbates long-term PM2.5 exposure-induced lung injury and cardiac dysfunction
复制标题
AMPK α 2 缺乏会加剧长期 PM2.5 暴露引起的肺损伤和心脏功能障碍
DOI：
10.1016/j.freeradbiomed.2018.05.008
复制
发表时间：
2018-06-01
影响因子：
7.4
通讯作者：
Lu, Zhongbing
中科院分区：
文献类型：
--
作者：
Wang, Hongyun;Shen, Xiyue;Lu, Zhongbing
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 AMPK alpha 2(-/-) mice to either airborne PM2.5 (mean daily concentration similar to 64 mu g/m(3)) or filtered air for 6 months through a whole-body exposure system. After exposure, AMPK alpha 2(-/-) mice developed severe lung injury and left ventricular dysfunction. In the PM(2.5)exposed lungs and hearts, loss of AMPK alpha 2 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 pNF-kappa B 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.
