Scortegagna M, Hanbauer I
Laboratory of Molecular Immunology, NHLBI, NIH, Bethesda, MD 20892-1674, USA.
Neurochem Res. 2000 Jun;25(6):861-6. doi: 10.1023/a:1007577710066.
Pb was shown to perturb neuronal and glial function either directly by interacting with protein thiol groups or indirectly by mimicking Ca(2+) and increasing oxidative stress. In view of the potential action of Pb on cellular redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA binding. A 1h incubation of astrocyte primary cultures with 10 microM Pb caused a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this increase revealed the involvement of 1. transcriptional and 2. posttranslational processes. The first one was documented by an increase of c-jun mRNA content after 15 to 30 min of 10 microM Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 microM Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1 signal transduction may regulate target genes operative in cell survival or cell death.
铅被证明可通过与蛋白质硫醇基团相互作用直接干扰神经元和神经胶质细胞功能，或通过模拟钙离子（Ca(2+)）并增加氧化应激间接干扰其功能。鉴于铅对细胞氧化还原稳态的潜在作用，我们研究了活化蛋白-1（AP-1）与DNA结合的调控。将原代星形胶质细胞培养物与10微摩尔的铅孵育1小时后，AP-1与DNA的结合增加了2.5倍。对铅如何引发这种增加的评估揭示了1.转录过程和2.翻译后过程的参与。第一个过程通过在暴露于10微摩尔铅15至30分钟后c-jun mRNA含量的增加得到证明。第二个过程通过在暴露于10微摩尔铅30至60分钟后氧化还原因子-1在细胞核中的积累增强得到暗示。铅引发的对氧化还原敏感的AP-1信号转导的增加可能调节在细胞存活或细胞死亡中起作用的靶基因。
