Association of increase in Serping1 level with dopaminergic cell reduction in an MPTP-induced Parkinson's disease mouse model.

Parkinson's disease (PD) is a progressive neurodegenerative disease, which shows distinct manifestations such as significant loss of dopaminergic neurons in the substantia nigra (SN). Gene expression was analyzed in the SN of mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), wherein downregulation of dopaminergic neurons occurred to examine the possible causes leading to the loss of dopaminergic neurons. In addition, a serine/cysteine protease inhibitor (Serping1) was studied as one of the genes that were prominently upregulated in mice chronically intoxicated with MPTP. Western blot analysis showed that, concomitant to the downregulation of dopaminergic cells, there was a substantial increase in Serping1 expression within the SN of the MPTP-induced PD mouse model. The SH-SY5Y cells were transfected with Serping1 short interfering RNA (siRNA) to evaluate the correlation between the expression of Serping1 and the loss of dopaminergic cells. Serping1 depletion elicited the upregulation of dopaminergic cells. Moreover, neuroprotective effect against dopaminergic cell loss was demonstrated upon the inhibition of Serping1 expression by siRNA in the MPP+ (1-methyl-4-phenylpyridinium)- treated SH-SY5Y cells. These results show that increased expression of Serping1 may play a critical role in dopaminergic cell death in the SN of chronic MPTP-induced PD mouse model and in SH-SY5Y cells.