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

Abstract

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.

Geranylgeranylacetone Ameliorates Skin Inflammation by Regulating and Inducing Thioredoxin via the Thioredoxin Redox System

“…Exogenous TRX activates transient receptor potential channels (TRPCs) to regulate intracellular calcium via thiol-modified redox mechanisms [ 51 , 52 ]. To verify the relationship between TRPCs and GGA-induced TRX, we treated PAM212 cells with SKF96365 (TRPC inhibitor) or U-73122 (phospholipase C inhibitor), together with GGA, and showed no significant change in TRX expression in the experimental versus control group (The data are shown in the Supplementary Material ); the relationship between calcium and TRX may be unidirectional or more relevant in neuronal cells.…”