Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutant cells

Abstract

DJ-1 is a novel oncogene and a causative gene for the familial form of Parkinson's disease (PD). DJ-1 has been shown to play roles in anti-oxidative stress by eliminating reactive oxygen species and in transcriptional regulation of genes. Loss of these functions of DJ-1 is thought to trigger the onset of PD. In this study, to identify genes for which expressions are regulated by DJ-1, DNA microarray analyses were carried out using two mouse NIH3T3 cell lines, DJ-1-knockdown cells and cells harboring an exogenously added L166P DJ-1 mutant found in PD patients. In both cell lines, drastic changes in expressions of genes, including genes related to stress, apoptosis, oxidative stress and neurotoxicity, were observed and changes in expressions were confirmed by RT-PCR. Of the genes identified, expression level of the extracellular superoxide dismutase (SOD3) gene was found to decrease in DJ-1-knockdown cells, while expressions of SOD1 and SOD2 genes did not change. Furthermore, expression of the tau gene, a gene whose product gives cells neurotoxicity by aggregation, was found to increase at its promoter level in L166P DJ-1 cells. These findings suggest that DJ-1 regulates expressions of genes for which functions are thought to be related to cell death or neurodegeneration.