Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, China.
Environ Pollut. 2020 Jun;261:114207. doi: 10.1016/j.envpol.2020.114207. Epub 2020 Feb 20.
Exposure to benzo(a)pyrene (BaP) has been shown to cause mitochondrial dysfunction and injury to neural cells. Resveratrol (RSV) has been studied as an antioxidant, anti-inflammatory, anti-apoptotic, and anticancer agent and can modulate mitochondrial function in vitro and in vivo. However, the molecular mechanisms underlying RSV's protection against mitochondrial dysfunction have not been fully elucidated. To investigate whether RSV can effectively prevent BaP-induced mitochondrial dysfunction, we tested the effects of RSV in primary neuronal models. Our results confirmed that neurons exhibited mitochondrial dysfunction and apoptosis in the mitochondrial pathway after BaP-treatment, and that pretreatment with RSV could reduce that dysfunction. Further, our results indicated that RSV pretreatment enhanced mitochondrial biogenesis via the AMPK/PGC-1α pathway and activated mitophagy via the PINK1-Parkin and AMPK/ULK1 pathways, thereby coordinating mitochondrial homeostasis. We also found that RSV could alleviate mitochondrial network fragmentation caused by BaP. This work provided insights into the role of RSV in preventing BaP-induced primary neuronal apoptosis in the mitochondrial pathway, mainly via regulation of mitochondrial biogenesis and mitophagy through AMPK pathway, thus maintaining the integrity of the mitochondrial network.
暴露于苯并(a)芘（BaP）已被证明会导致线粒体功能障碍和神经细胞损伤。白藜芦醇（RSV）已被研究为一种抗氧化剂、抗炎剂、抗凋亡剂和抗癌剂，可在体外和体内调节线粒体功能。然而，RSV 预防线粒体功能障碍的分子机制尚未完全阐明。为了研究 RSV 是否能有效预防 BaP 诱导的线粒体功能障碍，我们在原代神经元模型中测试了 RSV 的作用。我们的结果证实，神经元在 BaP 处理后表现出线粒体功能障碍和线粒体途径中的细胞凋亡，而 RSV 预处理可减少这种功能障碍。此外，我们的结果表明，RSV 通过 AMPK/PGC-1α 途径预先处理可增强线粒体生物发生，并通过 PINK1-Parkin 和 AMPK/ULK1 途径激活自噬，从而协调线粒体的动态平衡。我们还发现 RSV 可以减轻 BaP 引起的线粒体网络碎片化。这项工作深入了解了 RSV 通过 AMPK 途径调节线粒体生物发生和自噬来预防 BaP 诱导的线粒体途径中原发性神经元细胞凋亡中的作用，从而维持线粒体网络的完整性。
