AIM The aim of this study is to investigate the possible correlation between the expression of Nurrl gene and selective cell death of dopamine (DA) neurons. Nurrl ( nuclear receptor-related factor 1 ) is highly expres...AIM The aim of this study is to investigate the possible correlation between the expression of Nurrl gene and selective cell death of dopamine (DA) neurons. Nurrl ( nuclear receptor-related factor 1 ) is highly expressed in mesencephalic DA system and specifically required for development and survival of DArgic neurons, the cells primarily lost and aggressive degenerated in Parkinson’s disease (PD). METHODS Firstly, SK-N-SH cells, which do not express endogenous Nurrl, were transfected with the pBK-RSV-Nurrl plasmid by LipofectAMINE and selected by G418. The expression of Nurrl protein in SK-N-SH/Nurrl cells was determined by immunocytochemistry. The effect of Nurrl gene on cell proliferation was also investigated.展开更多
Background： Nurrl plays an essential role in the development, survival, and function maintenance ofmidbrain dopaminergic （DA） neurons, and it is a potential target for Parkinson＇s disease （PD）. Nurrl mRNA can be...Background： Nurrl plays an essential role in the development, survival, and function maintenance ofmidbrain dopaminergic （DA） neurons, and it is a potential target for Parkinson＇s disease （PD）. Nurrl mRNA can be detected in peripheral blood mononuclear cells （PBMCs）, but whether there is any association of altered Nurrl expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurrl mRNA level in PBMC and evaluate the effect of Nurrl expression by DA agents in vivo and in vitro. Methods： The mRNA levels of Nurrl in PBMC of four subgroups of 362 PD patients and 193 healthy controls （HCs） using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurrl expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurrl expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level. Results： The relative Nurrl mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments （de novo） （P 〈 0.001 ） and HC groups （P 〈 0.010）, respectively. Furthermore, the increase in Nurr I mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurrl mRNA expression level in PBMC. In vitlv, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurrl mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively （P 〈 0.001 ）. Conclusions： DA agonists can induce Nurrl expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.展开更多
文摘AIM The aim of this study is to investigate the possible correlation between the expression of Nurrl gene and selective cell death of dopamine (DA) neurons. Nurrl ( nuclear receptor-related factor 1 ) is highly expressed in mesencephalic DA system and specifically required for development and survival of DArgic neurons, the cells primarily lost and aggressive degenerated in Parkinson’s disease (PD). METHODS Firstly, SK-N-SH cells, which do not express endogenous Nurrl, were transfected with the pBK-RSV-Nurrl plasmid by LipofectAMINE and selected by G418. The expression of Nurrl protein in SK-N-SH/Nurrl cells was determined by immunocytochemistry. The effect of Nurrl gene on cell proliferation was also investigated.
基金grants from the National High Technology Research and Development Program of China，the State Key Development Program for Basic Research of China，the National Natural Science Foundation of China，key project from Guangzhou Science and Technology Department，Medical Scientific Research Foundation of Guangdong Province,China，Medicine and Health Care Technology Projects Foundation of Guangzhou City,China
文摘Background： Nurrl plays an essential role in the development, survival, and function maintenance ofmidbrain dopaminergic （DA） neurons, and it is a potential target for Parkinson＇s disease （PD）. Nurrl mRNA can be detected in peripheral blood mononuclear cells （PBMCs）, but whether there is any association of altered Nurrl expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurrl mRNA level in PBMC and evaluate the effect of Nurrl expression by DA agents in vivo and in vitro. Methods： The mRNA levels of Nurrl in PBMC of four subgroups of 362 PD patients and 193 healthy controls （HCs） using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurrl expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurrl expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level. Results： The relative Nurrl mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments （de novo） （P 〈 0.001 ） and HC groups （P 〈 0.010）, respectively. Furthermore, the increase in Nurr I mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurrl mRNA expression level in PBMC. In vitlv, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurrl mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively （P 〈 0.001 ）. Conclusions： DA agonists can induce Nurrl expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.
