Graduate School of Environmental Science, Hokkaido University, Sapporo 060-0810, Japan.
Laboratory of Environmental Health Science, Faculty of Health Science, Hokkaido University, Sapporo 060-0812, Japan; Group of Environmental Adaptation Science, Faculty of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan; Department of Public Health and Informatics, Jahangirnagar University, Dhaka 1342, Bangladesh.
Food Chem Toxicol. 2018 Apr;114:180-189. doi: 10.1016/j.fct.2018.02.034. Epub 2018 Feb 15.
Purpose of this study is to investigate mechanism/s of cyto-protection by selenium (NaSeO; Se) against cadmium (CdCl; Cd)-induced cytotoxicity using PC12 cells. In addition, Se (5, 10, 20 and 40 μM) and Cd (2.5, 5 and 10 μM)-induced cytotoxicity is determined. Cytotoxicity assays and western blot analyses confirmed that Se (≥10 μM) promotes autophagic cell death via inhibition of mTOR activation and p62 accumulation due to increase of cellular oxidative stress. On the other hand, co-presence of non-toxic Se (5 μM) and toxic Cd (5 μM) showed to increase cell viability, glutathione and glutathione peroxidase 1 (GPx1) levels, and to decrease DNA fragmentation and lactate dehydrogenase (LDH) activity compared to Cd-treated (5 μM) cells alone. Furthermore, western blot analyses of cytochrome c and ERK1 indicated that Cd-induced apoptotic cell death in PC12 cells. However, the co-exposure of Se with Cd significantly decreases the release of cytochrome c into cytosol from mitochondria, and up-regulates ERK1 protein to inhibit Cd-induced apoptosis. In conclusion, Se (≥10 μM) possess cytotoxicity in PC12 cells; however, co-presence of Se (5 μM) with Cd (5 μM) protects against Cd-induced apoptosis in PC12 cells due to inhibition of Cd-induced oxidative stress and subsequently suppression of mitochondrial apoptosis pathway.
本研究旨在探讨硒（NaSeO；Se）对镉（CdCl；Cd）诱导的 PC12 细胞毒性的细胞保护机制。此外，还确定了 Se（5、10、20 和 40μM）和 Cd（2.5、5 和 10μM）诱导的细胞毒性。细胞毒性测定和 Western blot 分析证实，Se（≥10μM）通过抑制 mTOR 激活和 p62 积累，从而增加细胞氧化应激，促进自噬性细胞死亡。另一方面，与单独用 Cd（5μM）处理的细胞相比，非毒性 Se（5μM）和毒性 Cd（5μM）的共存显示出增加细胞活力、谷胱甘肽和谷胱甘肽过氧化物酶 1（GPx1）水平，并降低 DNA 片段化和乳酸脱氢酶（LDH）活性。此外，细胞色素 c 和 ERK1 的 Western blot 分析表明，Cd 在 PC12 细胞中诱导了凋亡性细胞死亡。然而，Se 与 Cd 的共暴露显著减少了线粒体中细胞色素 c 向细胞质的释放，并上调了 ERK1 蛋白，从而抑制了 Cd 诱导的凋亡。总之，Se（≥10μM）在 PC12 细胞中具有细胞毒性；然而，Se（5μM）与 Cd（5μM）的共存可防止 Cd 诱导的 PC12 细胞凋亡，这归因于抑制 Cd 诱导的氧化应激，进而抑制线粒体凋亡途径。
