Abstract
Oxidative stress-induced dopaminergic neuronal loss and apoptosis play a crucial role in the pathogenesis of Parkinson’s disease (PD), and as a vital antioxidant protein, thioredoxin (Trx) exerts neuroprotection against PD. In this study, we investigated the effect of Schisanhenol (Sal), an active component from a traditional Chinese herb Schisandra rubriflora (Franch.), on MPP+-induced apoptosis and its association with thioredoxin-1 (Trx1) in SH-SY5Y cells. The protein levels of Trx1 and apoptosis-related proteins were detected by Western blot, the expression of Trx1 mRNA by real time qPCR, and apoptosis was detected by fluorescence microscopy and flow cytometry. Pretreatment with Sal (1 µM, 10 µM, and 50 µM) dose-dependently ameliorated MPP+-induced neuronal injury, confirmed by the improvement of the viability and morphological changes. Sal decreased the apoptosis rate of cells, suppressed the production of DNA ladder and sub-G1 peak, inhibited the Caspase-3 activity and the expression of apoptosis-related proteins. Sal enhanced the expression of Trx1 both in the protein and mRNA levels. However, the Trx1 inhibitor PX-12 suppressed the protective effects of Sal. In addition, Sal inhibited NF-κB translocation and activation. These results suggest that Sal has a protective effect against MPP+-induced apoptosis in SH-SY5Y cells via up-regulation of Trx1 expression and suppression of ASK1-P38-NF-κB pathway.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive motor disorder and loss of dopaminergic neurons in the substantia nigra pars compacta[1,2]
The present study demonstrated that Sal, an active component from a traditional Chinese herb Schisandra rubriflora (Franch.), dose-dependently protected SH-SY5Y cells against MPP+-induced apoptosis, and Trx[1] was involved in the neuroprotection of Sal
The results of the Hoechst 33,342 staining assay, the nuclear morphological analysis, and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining by flow cytometric analysis, cell cycle, and DNA fragmentation, demonstrated that the neuroprotection of Sal at least partly comes from its anti-apoptotic effects
Summary
Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive motor disorder and loss of dopaminergic neurons in the substantia nigra pars compacta[1,2]. DJ-1-induced Trx[1] protected SH-SY5Y cells and substantia nigra of mice from oxidative stress[11]. Trx exerted neuroprotection against oxidative stress-induced apoptosis in SH-SY5Y cells[14], decreased the formation of α-Synuclein inclusions[15]. These results suggest that Trx or Trx inducer is a potential new therapeutic agent for PD. We aimed to investigate the neuroprotective effect of Sal against M PP+-induced apoptosis, as well as explore the underlying mechanisms of Sal in human neuroblastoma SH-SY5Y cells, to elucidate whether Trx[1] is one of the molecular targets of Sal
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