Troops of 95935 Unit Haerbin, PR China.
Cell Signal. 2013 May;25(5):1126-35. doi: 10.1016/j.cellsig.2013.02.003. Epub 2013 Feb 10.
The osteoblasts could be lead to the occurrence of apoptosis by oxidative stress. The zinc transporter family SLC30A (ZnTs) plays an important role in the regulation of zinc homeostasis, however, its function in apoptosis of MC3T3-E1 cells remains unknown. This study was aimed to investigate the role of zinc transporters in cell survival, particularly in MC3T3-E1 cells, during oxidative stress, and the molecular mechanism involved. Our study found that hydrogen peroxide can induce zinc-overloaded in the cells. While high concentration of zinc plays an important role in inducing apoptosis of the MC3T3-E1 cells, we demonstrated that ZnT7 can protect MC3T3-E1 cells and reduce the aggregation of intracellular free zinc ions as well as inhibit apoptosis induced by H2O2. Moreover, ZnT7 overexpression enhanced the anti-apoptotic effects. Interestingly, suppression of ZnT7 by siRNA could significantly exacerbate apoptosis in MC3T3-E1 cells. We also found that ZnT7 promotes cell survival via two distinct signaling pathways involving activation of the PI3K/Akt-mediated survival pathway and activation of MAPK/ERK pathway. Collectively, these results suggest that ZnT7 overexpression significantly protects osteoblasts cells from apoptosis induced by H2O2. This effect is mediated, at least in part, through activation of PI3K/Akt and MAPK/ERK pathways.
氧化应激可导致成骨细胞发生细胞凋亡。锌转运体家族 SLC30A（ZnTs）在锌稳态调节中发挥重要作用，但其在 MC3T3-E1 细胞凋亡中的作用尚不清楚。本研究旨在探讨锌转运体在细胞存活中的作用，特别是在 MC3T3-E1 细胞中，以及涉及的分子机制。我们的研究发现，过氧化氢可诱导细胞内锌超载。虽然高浓度的锌在诱导 MC3T3-E1 细胞凋亡中起重要作用，但我们证明 ZnT7 可保护 MC3T3-E1 细胞并减少细胞内游离锌离子的聚集，同时抑制 H2O2 诱导的细胞凋亡。此外，ZnT7 的过表达增强了抗凋亡作用。有趣的是，通过 siRNA 抑制 ZnT7 可显著加剧 MC3T3-E1 细胞的凋亡。我们还发现，ZnT7 通过两条不同的信号通路促进细胞存活，涉及激活 PI3K/Akt 介导的存活途径和 MAPK/ERK 途径的激活。总之，这些结果表明，ZnT7 的过表达可显著保护成骨细胞免受 H2O2 诱导的细胞凋亡。这种作用至少部分是通过激活 PI3K/Akt 和 MAPK/ERK 途径介导的。
