Sun Yongkun, Liu Chuang, Liu Yutong, Hosokawa Toshiyuki, Saito Takeshi, Kurasaki Masaaki
a Group of Environmental Adaptation Science, Faculty of Environmental Earth Science, Hokkaido University , Sapporo , Japan.
J Environ Sci Health A Tox Hazard Subst Environ Eng. 2014;49(9):1023-8. doi: 10.1080/10934529.2014.894847.
Despite extensive research on copper toxicity the mechanisms involved are not fully characterized. There have been many recent reports concerning the relationship between epigenetic factors and cell metabolism, but the effects of copper exposure on epigenetic factors have not been investigated. In this study, an in vitro culture system was employed to study the influence of copper on apoptosis and epigenetic factors in PC12 cells. When PC12 cells were exposed to copper, DNA damage was observed as DNA fragmentation. In addition, cytosolic cytochrome c levels were increased by copper treatment. These results suggested that copper induced apoptosis via an oxidative stress pathway. This was consistent with the observation that copper-induced apoptosis was enhanced by further oxidative stress induced by exposing cells to H₂O₂. In addition, the epigenetic factors were significantly increased in apoptotic cells following exposure to copper and oxidative stress.
尽管对铜毒性进行了广泛研究，但其中涉及的机制尚未完全明确。最近有许多关于表观遗传因素与细胞代谢之间关系的报道，但铜暴露对表观遗传因素的影响尚未得到研究。在本研究中，采用体外培养系统来研究铜对PC12细胞凋亡和表观遗传因素的影响。当PC12细胞暴露于铜时，观察到DNA损伤表现为DNA片段化。此外，铜处理可使细胞溶质细胞色素c水平升高。这些结果表明铜通过氧化应激途径诱导细胞凋亡。这与以下观察结果一致，即通过将细胞暴露于H₂O₂诱导进一步的氧化应激可增强铜诱导的细胞凋亡。此外，在暴露于铜和氧化应激后的凋亡细胞中，表观遗传因素显著增加。
