Department of Cellular Signalling, M. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Folia Neuropathol. 2011;49(4):319-27.
Systemic exposure of rodents to the herbicide paraquat (PQ) was suggested to reproduce pathological features of Parkinson's disease. Our recent data showed that long-term PQ administration influenced levels of glycogen synthase kinase 3β (GSK-3β) and its active form phosphorylated on tyrosine 216 in the nigrostriatal system, which may be related to its vulnerability to PQ toxicity. The aim of this study was to analyse selectivity of the toxic effect of PQ after its systemic administration in rats. PQ was administered for 37 weeks and the protein level of total GSK-3β and its active GSK-3β (pY216) form in subcellular fractions of hippocampus, brain cortex and cerebellum was examined. Our data indicated that the long-term administration of PQ significantly decreased the level of both GSK-3β forms in nuclear and cytosolic fractions of hippocampus in rats. In the brain cortex and cerebellum PQ decreased the level of both forms of GSK-3β in the nuclear fraction but increased their levels in mitochondria and in some cases also in the cytosol. The results of the present study indicate that PQ influenced levels and activation of GSK-3β in different brain structures, which may contribute to its toxicity, but on the other hand may suggest development of adaptive, protective mechanisms.
长期接触百草枯会导致啮齿动物出现类似于帕金森病的病理特征。我们最近的数据表明，长期给予百草枯会影响黑质纹状体系统中糖原合成酶激酶 3β（GSK-3β）及其酪氨酸 216 磷酸化的活性形式的水平，这可能与其对百草枯毒性的易感性有关。本研究旨在分析百草枯在系统性给药后对其毒性作用的选择性。给予百草枯 37 周后，分析海马体、大脑皮层和小脑亚细胞部分中总 GSK-3β及其活性 GSK-3β（pY216）形式的蛋白水平。我们的数据表明，长期给予百草枯会显著降低大鼠海马体核和胞质部分中两种 GSK-3β 形式的水平。在大脑皮层和小脑，百草枯降低了核部分中两种 GSK-3β 形式的水平，但增加了它们在线粒体中的水平，在某些情况下也增加了在细胞质中的水平。本研究的结果表明，百草枯影响了不同脑结构中 GSK-3β 的水平和激活，这可能导致其毒性，但另一方面可能表明适应性、保护机制的发展。
