Thioredoxin-1 regulates calcium homeostasis in MPP⁺ /MPTP-induced Parkinson's disease models

Disturbance in calcium (Ca²⁺ ) homeostasis has been involved in a variety of neuropathological conditions including Parkinson's disease (PD). The Ca²⁺ channel, transient receptor potential channel 1 (TRPC1), plays a protective role in regulating entry of Ca²⁺ activated by store depletion of Ca²⁺ in endoplasmic reticulum (ER). We have showed that thioredoxin-1 (Trx-1) plays a role in suppressing ER stress in PD. However, whether Trx-1 regulates TRPC1 expression in PD is still unknown. In the present study, we demonstrated that treatment of 1-methyl-4-phenylpyridinum ion (MPP⁺ ) significantly reduced the expression of TRPC1 in PC12 cells, which was restored by Trx-1 overexpression, and further decreased significantly by Trx-1 siRNA. Moreover, we found that Ca²⁺ entered into the cells was decreased by MPP⁺ in PC 12 cells, which was restored by Trx-1 overexpression, and further decreased by Trx-1 siRNA. MPP⁺ significantly increased calcium-dependent cysteine protease calpain1 expression in PC12 cells, which was suppressed by Trx-1 overexpression. Calpain1 expression was increased by Trx-1 siRNA or SKF96365, an inhibitor of TRPC1. Moreover, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased TRPC1 expression in the substantia nigra pars compacta region (SNpc), which was restored in mice overexpressing Trx-1, and further decreased in mice of knockdown Trx-1. Inversely, the expression of calpain1 was increased by MPTP, which was suppressed in mice overexpressing Trx-1, and further increased in mice of knockdown Trx-1. In conclusion, Trx-1 regulates the Ca²⁺ entry through regulating TRPC1 expression after treatment of MPP⁺ /MPTP.