College of Environment and Resource, Center of Environmental Science and Engineering, Shanxi University, Taiyuan, Shanxi, People's Republic of China.
Inhal Toxicol. 2010 Sep;22(11):919-29. doi: 10.3109/08958378.2010.494694.
The possible neurotoxicity of SO(2) has been implicated by determining morphological change, oxidative stress, DNA damage and membrane channel alteration in previous studies, however, its detailed mechanisms remain unclear. In the present study, we investigated SO(2) inhalation-induced effects on the transcription and translation of several apoptosis-related genes (p53, bax, bcl-2, c-fos, and c-jun) in rat hippocampus, using real-time RT-PCR analysis and western blotting technique, respectively. The results demonstrate that SO(2) statistically increased p53 expression and the ratio of bax to bcl-2 in a concentration-dependent manner. Also, mRNA and protein levels of c-fos and c-jun significantly elevated in proportion to exposure concentration. Then, we treated primary cultured hippocampal neurons with SO(2) derivatives (bisulfite and sulfite, 3:1 M/M), and examined mRNA levels of above genes. The results show that P53, c-fos, c-jun mRNA expression and the ratio of bax to bcl-2 augmented as functions of SO(2) derivative concentration and exposure time, and confirm that SO(2) affected the transcription and translation process of apoptosis-related genes in central nervous system via its derivatives in vivo. The present data provide further evidence for SO(2)-caused neurological insults, and imply that two major pathways associated with p53 and AP-1 might play important roles in the pathogenesis.
先前的研究通过确定形态变化、氧化应激、DNA 损伤和膜通道改变，暗示了 SO(2)可能具有神经毒性，但其详细机制尚不清楚。在本研究中，我们分别使用实时 RT-PCR 分析和 Western blot 技术，研究了 SO(2)吸入对大鼠海马中几种凋亡相关基因（p53、bax、bcl-2、c-fos 和 c-jun）的转录和翻译的影响。结果表明，SO(2)以浓度依赖的方式显著增加了 p53 的表达和 bax 与 bcl-2 的比值。此外，c-fos 和 c-jun 的 mRNA 和蛋白水平也相应地随暴露浓度升高而增加。然后，我们用 SO(2)衍生物（亚硫酸氢盐和亚硫酸盐，摩尔比为 3:1）处理原代培养的海马神经元，并检测了上述基因的 mRNA 水平。结果表明，P53、c-fos、c-jun mRNA 表达和 bax 与 bcl-2 的比值随 SO(2)衍生物浓度和暴露时间的增加而增加，证实了 SO(2)通过其衍生物影响中枢神经系统中凋亡相关基因的转录和翻译过程。本数据为 SO(2)引起的神经损伤提供了进一步的证据，并表明与 p53 和 AP-1 相关的两个主要途径可能在发病机制中发挥重要作用。
