砷以三价和五价形式广泛存在于环境中;由于环境污染而长期暴露于砷已成为一个问题。先前的报道表明,在产生EPO的HepG2细胞中,暴露于砷酸盐(作为五价砷)的24小时可通过活性氧(ROS)增强促红细胞生成素(EPO)的产生。然而,长期砷酸盐暴露对EPO产生的影响尚不清楚.在砷酸盐存在下传代培养3周的HepG2细胞中,EPOmRNA水平低于未处理的细胞。砷甲基转移酶mRNA水平,以及核因子类红细胞相关因子2,谷胱甘肽,和超氧化物歧化酶蛋白,与未处理的细胞相比,但丙二醛水平没有显著改变。因此,长期暴露于砷酸盐可增强ROS清除能力,表明砷酸盐暴露减弱了ROS诱导的EPOmRNA积累。长期的砷酸盐暴露也减弱了缺氧对EPO积累的诱导,表明EPO生产的响应性受到损害。此外,影响EPO转录的SIRTUIN-1的mRNA水平,长期砷酸盐暴露会增强。这些结果表明,长期暴露于砷酸盐有多个,在体外对EPO产生不同的影响。
Arsenic is widely present in the environment in trivalent and pentavalent forms; long-term arsenic exposure due to environmental pollution has become a problem. Previous reports have shown that 24-h exposure to
arsenate (as pentavalent arsenic) potentiates erythropoietin (EPO) production via reactive oxygen species (ROS) in EPO-producing HepG2 cells. However, the effects of long-term
arsenate exposure on EPO production remain unclear. In HepG2 cells subcultured for 3 weeks in the presence of
arsenate, EPO mRNA levels were lower than those in untreated cells. Levels of ARSENITE METHYLTRANSFERASE mRNA, as well as those of Nuclear factor erythroid 2-related factor 2, glutathione, and superoxide dismutase proteins, were increased compared to untreated cells, but levels of malondialdehyde were not significantly altered. Thus, long-term exposure to arsenate enhances ROS scavenging, suggesting that the ROS-induced accumulation of EPO mRNA is attenuated by
arsenate exposure. The induction of EPO accumulation by hypoxia also was attenuated by long-term arsenate exposure, suggesting an impairment in responsivity of EPO production. Furthermore, mRNA levels of SIRTUIN-1, which affects EPO transcription, were potentiated by long-term arsenate exposure. These results suggest that long-term
arsenate exposure has multiple, distinct effects on EPO production in vitro.