Gene expression profiles regulated by Hspa1b in MPTP-induced dopaminergic neurotoxicity using knockout mice

Heat shock proteins 70 (Hsp70), a chaperone that is up-regulated in stress responses and that refolds proteins, might be involved in the pathogenesis of Parkinson disease (PD). This study examined the gene expression profiling regulated by the Hsp70 gene using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated PD model of mice. The differences in gene expression after a MPTP treatment in C57BL/6 normal mice and Hspa1b (Hsp70-1) knockout (KO) mice was compared using a 24K cDNA microarray. Microarray analysis showed that 246 genes were expressed differentially by the MPTP treatment in normal mice (147 up-regulated and 279 down-regulated). The MPTP-treated KO mice resulted in the differential expression of 26 genes (12 up-regulated and 13 down-regulated) compared to the MPTP-treated normal mice group. The PANTHER database was used to evaluate the microarray data. A total of 38 signaling pathways involved in 426 differentially expressed genes as a result of the MPTP treatment in normal mice were significant. Of these 38 pathways, the pathways related to 25 genes changed by a Hspa1b deficiency were 5-Hydroxytryptamine biosynthesis, adrenaline and noradrenaline biosynthesis, and Parkinson disease. These results demonstrated various genes regulated by Hspa1b in a MPTP-induced PD model. In conclusion, we suggest that this study may be partly helpful to identify action mechanism in the development of a novel drug targeted to Hspa1b gene in the treatment of PD.