摘要
为解释糖尿病型帕金森病的分子机理,利用LC-ESI-TOF与LC-ESI-MS/MS联用的比较蛋白质组学方法,分析了链脲霉素诱导的糖尿病大鼠模型与对照大鼠的纹状体、海马区蛋白的表达差异,通过定量比较发现有23种蛋白表达水平发生了2倍以上的显著变化。其中包括与帕金森病致病通路(兴奋性中毒)密切相关的兴奋性氨基酸转运蛋白,与自由基清除、氧化应激密切相关的超氧化物歧化酶,以及与能量合成密切相关的线粒体ATP合酶。发现参与糖酵解过程的7种酶也发生了不同程度的表达变化,提示可能与内源性神经毒素1-乙酰基-6,7-二羟基-1,2,3,4-四氢异喹啉的生成与累积密切相关。
Diabetes is a risk factor for Parkinson' s disease (PD). There are statistics data indicating that the prevalence of PD among patients with diabetes was higher compared with the normal people. To date, little is known about the molecular events underlying hyperglycemia-induced PD. Here, the proteins of corpus striatum (ST) and hippocampus from the brains of diabetes rat models and control rats were analyzed by comparing proteomics method. LC-ESI-TOF and LC- ESI-MS/MS were used for analysis. It was found that 23 express levels of proteins, in which including excitatory amino acid transporter, ATP synthase and superoxide dismutase (SOD), were significantly changed in the experiments. It was also found that seven key enzymes which occurred in glycolysis pathway increased significantly in diabetes rat model brains, which mean that the endogenous neurotoxin ADTIQ concentration perhaps had been enhanced. These results indicated that the express levels of several proteins close related to PD which changed under hyperglycemia condition, and it supports the view that diabetes is a risk factor for Parkinson's disease.
出处
《化学通报》
CAS
CSCD
北大核心
2008年第6期430-434,共5页
Chemistry
基金
国家自然科学基金项目(20435020)资助