Abstract
The cold shock protein RBM3 can mediate mild hypothermia-related protection in neurodegeneration such as Alzheimer's disease. However, it remains unclear whether RBM3 and mild hypothermia provide same protection in model of Parkinson's disease (PD), the second most common neurodegenerative disorder. In this study, human SH-SY5Y neuroblastoma cells subjected to insult by 1-methyl-4-phenylpyridinium (MPP+) served as an in-vitro model of PD. Mild hypothermia (32°C) aggravated MPP+-induced apoptosis, which was boosted when RBM3 was silenced by siRNA. In contrast, overexpression of RBM3 significantly reduced this apoptosis. MPP+ treatment downregulated the expression of RBM3 both endogenously and exogenously and suppressed its induction by mild hypothermia (32°C). In conclusion, our data suggest that cold shock protein RBM3 provides neuroprotection in a cell model of PD, suggesting that RBM3 induction may be a suitable strategy for PD therapy. However, mild hypothermia exacerbates MPP+-induced apoptosis even that RBM3 could be synthesized during mild hypothermia.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide
The gene expression of RBM3 at transcriptional level is sensitive to MPP+ treatment. 1, 2, and 3 mM MPP+ post 24 h exposure reduced mRNA expression of RBM3 by 47.7, 69.7, and 71.3% compared to control (Figure 1B)
With the increase in the concentration of MPP+, RBM3 protein was gradually downregulated and the reduction was most pronounced at 3 mM MPP+ exposure
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide (de Lau and Breteler, 2006). It is featured by a progressive loss of dopaminergic neurons in substantia nigra pars compacta (Spillantini et al, 1997). Nigral dopaminergic cellular apoptosis and mitochondrial dysfunction induced by various factors may play a critical role in the neurodegenerative processes in PD, the etiology of PD remains elusive (Yuan and Yankner, 2000; Lin and Beal, 2006; Yang et al, 2010). Researchers are searching for factors, as yet undiscovered, that could prevent dopaminergic neuronal apoptosis and serve as possible therapeutic strategies of PD Hypothermia can reduce neuronal death in neurodegenerative disease, which is known to involved the progressive
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