Biomass-related PM2.5 induces mitochondrial fragmentation and dysfunction in human airway epithelial cells*
Biomass-related PM2.5 induces mitochondrial fragmentation and dysfunction in human airway epithelial cells*
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DOI：
10.1016/j.envpol.2021.118464
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发表时间：
2021-11-10
影响因子：
8.9
通讯作者：
Ran, Pixin
中科院分区：
文献类型：
--
作者：
Gao, Mi;Liang, Chunxiao;Ran, Pixin
使用生物质进行烹饪和取暖被认为是与慢性阻塞性肺病（COPD）相关的一个重要因素，但此前很少有研究探讨其潜在机制。因此，本研究旨在评估生物量相关的 PM2.5 (BRPM2.5) 暴露对 16HBE 人类气道上皮细胞和小鼠线粒体功能障碍的影响。我们的研究表明，16HBE 细胞暴露于 BRPM2.5 会导致线粒体功能障碍，包括线粒体膜电位降低、裂变蛋白磷酸化 DRP1 表达增加、线粒体 ROS (mtROS) 增加和 ATP 水平降低。 BRPM2.5 通过减少线粒体耗氧量和糖酵解来改变 16HBE 细胞的线粒体代谢。然而，线粒体靶向肽 SS-31 消除了线粒体 ROS，减轻了 ATP 缺乏和促炎细胞因子的释放。 BRPM2.5 暴露导致 16HBE 和肺组织中线粒体形态发生异常改变。综上所述，这些结果表明 BRPM2.5 对人类气道上皮细胞具有有害影响，导致线粒体功能障碍、线粒体代谢异常和线粒体动力学改变。本研究提供了第一个证据，证明线粒体结构和线粒体代谢的破坏可能是 BRPM2.5 诱导的呼吸功能障碍的机制之一。
The use of biomass for cooking and heating is considered an important factor associated with chronic obstructive pulmonary disease (COPD), but few studies have previously addressed its underlying mechanisms. Therefore, this research aimed to evaluate the effects of biomass-related PM2.5 (BRPM2.5) exposure on 16HBE human airway epithelial cells and in mice with regard to mitochondrial dysfunction. Our study indicated that BRPM2.5 exposure of 16HBE cells resulted in mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased expression of fission proteins-phospho-DRP1, increased mitochondrial ROS (mtROS), and decreased levels of ATP. BRPM2.5 altered the mitochondrial metabolism of 16HBE cells by decreasing mitochondrial oxygen consumption and glycolysis. However, Mitochondria targeted peptide SS-31 eliminated mitochondrial ROS and alleviated the ATP deficiency and proinflammatory cytokines release. BRPM2.5 exposure resulted in abnormal mitochondrial morphological alterations both in 16HBE and in lung tissue. Taken together, these results suggest that BRPM2.5 has detrimental effects on human airway epithelial cells, leading to mitochondrial dysfunction, abnormal mitochondrial metabolism and altered mitochondrial dynamics. The present study provides the first evidence that disruption of mitochondrial structure and mitochondrial metabolism may be one of the mechanisms of BRPM2.5-induced respiratory dysfunction.