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Int. J. Mol. Sci. 2014, 15(8), 13209-13222; doi:10.3390/ijms150813209

Chikusetsu Saponin V Attenuates MPP+-Induced Neurotoxicity in SH-SY5Y Cells via Regulation of Sirt1/Mn-SOD and GRP78/Caspase-12 Pathways

1
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China
2
Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, Yichang 443002, China
3
Institute of Molecular Biology, China Three Gorges University, Yichang 443002, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 20 April 2014 / Revised: 5 June 2014 / Accepted: 16 June 2014 / Published: 28 July 2014
(This article belongs to the Section Molecular Toxicology)
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Abstract

Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects. View Full-Text
Keywords: Chikusetsu saponin V; MPP+; Sirt1; GRP78 Chikusetsu saponin V; MPP+; Sirt1; GRP78
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Yuan, D.; Wan, J.-Z.; Deng, L.-L.; Zhang, C.-C.; Dun, Y.-Y.; Dai, Y.-W.; Zhou, Z.-Y.; Liu, C.-Q.; Wang, T. Chikusetsu Saponin V Attenuates MPP+-Induced Neurotoxicity in SH-SY5Y Cells via Regulation of Sirt1/Mn-SOD and GRP78/Caspase-12 Pathways. Int. J. Mol. Sci. 2014, 15, 13209-13222.

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