The Effect of Dopamine on Gene Expression of Alpha-synuclein and Transcription Factors GATA-1, GATA-2, and ZSCAN21 in Parkinson’s Disease

Abstract

At present, it is believed that disregulation of alpha-synuclein (SNCA) metabolism and its aggregation is associated with the pathogenesis of Parkinson’s disease (PD). It is thought that the death of dopaminergic neurons in PD can be mediated by the effect of dopamine on the process of alpha-synuclein oligomerization, primarily by direct oxidation of the protein. At the same time, the effect of dopamine on the regulation mechanism of the SNCA gene expression is not excluded. It is known that transcription factors GATA-1, GATA-2, and ZSCAN21 can participate in the regulation of SNCA expression. In the present study, we evaluated the effect of exogenous dopamine (100 μM) on the mRNA level of the SNCA, GATA-1, GATA-2, and ZSCAN21 genes and the level of total alpha-synuclein in cultured peripheral blood lymphocytes (PBL) of patients with PD (n = 18) and individuals of the control group (n = 14) using real-time PCR and ELISA, subsecuently. A decrease in the SNCA expression level under the action of dopamine was first found in PBL of patients with PD (P = 0.013), of the control group (P = 0.004), and of the combined group that included patients with PD and control individuals (P = 0.001). When assessing alpha-synuclein level, a tendency toward its decrease in PBL of individuals from the control group (P = 0.068), as well as of the combined group of PD patients and control individuals (P = 0.059), was revealed by comparing the cells treated and untreated with dopamine. An increase in the mRNA level of the ZSCAN21 gene in PBL of control group individuals (P = 0.022), as well as of the GATA-1 gene in PBL of the group of patients with PD (P = 0.019) cultured in the presence of dopamine, was shown. An increase in the mRNA levels of the genes GATA-1, GATA-2, and ZSCAN21 in PBL under the treatment with dopamine was also observed in the combined group of patients with PD and control individuals (P = 0.027, 0.029, and 0.002 for GATA-1, GATA-2, and ZSCAN21, respectively). Thus, the obtained data show the effect of dopamine on the mRNA level of the SNCA, GATA-1, GATA-2, and ZSCAN21 genes in cultured PBL of PD patients and control group individuals, suggesting a possible effect of dopamine on the regulation of SNCA expression.