Synphilin-1 has neuroprotective effects on MPP+-induced Parkinson's disease model cells by inhibiting ROS production and apoptosis. (18th January 2019)

• Record Type: Journal Article
• Authors: Shishido, Takeo; Nagano, Yoshito; Araki, Mutsuko; Kurashige, Takashi; Obayashi, Hitomi; Nakamura, Takeshi; Takahashi, Tetsuya; Matsumoto, Masayasu; Maruyama, Hirofumi
• Is Part Of: Neuroscience letters. Volume 690(2019)
• Page Start: 145
• Page End: 150
• Publication Date: 2019-01-18
• Subjects: PD Parkinson's disease -- DAergic dopaminergic -- LBs Lewy bodies -- Tg transgenic -- LRRK2 leucine-rich repeat kinase 2 -- DA dopamine -- MPTP 1-methyl-4-phenyl-12, 3, 6-tetrahydropyridine -- MPP+ 1-methyl-4-phenylpyridinium -- ROS reactive oxygen species -- EV empty vector -- EDTA ethylenediaminetetraacetic acid -- DAPI 4′6-diamidino-2-phenylindole -- PARP poly-ADP-ribose polymerase -- DCFDA 2′7′-dichlorodihydrofluorescein diacetate -- SEM standard error of the mean -- ANOVA analysis of variance -- Tukey's HSD test Tukey's honest significant difference test -- ATP adenosine triphosphate; Parkinson's disease -- synphilin-1 -- MPP+ -- Apoptosis -- Dopaminergic neurodegeneration; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.10.020
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Synphilin-1 inhibited ROS production and cytochrome c release induced by MPP + in vitro. Synphilin-1 inhibited early steps in the intrinsic apoptotic pathway. Synphilin-1 played a neuroprotective role in Parkinson's disease model cells. Abstract: Synphilin-1, a cytoplasmic protein, interacts with α-synuclein which is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease (PD), in neurons. This interaction indicates that synphilin-1 may also play a central role in PD. However, the biological functions of synphilin-1 are not fully understood, and whether synphilin-1 is neurotoxic or neuroprotective remains controversial. This study examined the function of synphilin-1 in a PD model in vitro. We used an inhibitor of mitochondrial complex I, 1-methyl-4-phenylpyridinium (MPP + ). We established human neuroblastoma SH-SY5Y cell lines that stably expressed human synphilin-1. We found that overexpression of synphilin-1 increased SH-SY5Y cell viability after MPP + treatment. We further found that synphilin-1 significantly suppressed apoptotic changes in nuclei, including nuclear condensation and fragmentation, after MPP + treatment. We showed that synphilin-1 significantly decreased MPP + -induced cleaved caspase-3 and cleaved poly-ADP-ribose polymerase levels by using western blotting. Production of reactive oxygen species (ROS) induced by MPP + was significantly reduced in cells expressing synphilin-1 compared to those expressing empty vector. Synphilin-1 inhibited MPP + -induced cytochrome c release from mitochondria into the cytosol. These data suggested that synphilin-1 may function to protect against dopaminergic cell death by preserving mitochondrial function and inhibiting early steps in the intrinsic apoptotic pathway. Taken together, our results indicated that synphilin-1 may play neuroprotective roles in PD pathogenesis by inhibiting ROS production and apoptosis.