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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 Jul 28; 15(8):13209-22.IJ

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.

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Authors+Show Affiliations

Yuan D
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. yxyydyd@126.com.
Wan JZ
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. 15071798496@163.com.
Deng LL
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. denglili3748@163.com.
Zhang CC
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. greatwall@ctgu.edu.cn.
Dun YY
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. dyw891122@163.com.
Dai YW
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. dyw891122@163.com.
Zhou ZY
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. in_bud@ctgu.edu.cn.
Liu CQ
Institute of Molecular Biology, China Three Gorges University, Yichang 443002, China. ctgulcq@163.com.
Wang T
Department of Pharmacology, College of Medical Science, China Three Gorges University, Yichang 443002, China. tingting0301@126.com.

MeSH

1-Methyl-4-phenylpyridiniumApoptosisCaspase 12Cell Line, TumorDown-RegulationEndoplasmic Reticulum StressHeat-Shock ProteinsHumansMembrane Potential, MitochondrialNeuroprotective AgentsProto-Oncogene Proteins c-bcl-2Reactive Oxygen SpeciesSaponinsSirtuin 1Superoxide DismutaseUp-Regulationbcl-2-Associated X Protein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25073091

Citation

Yuan, Ding, et al. "Chikusetsu Saponin V Attenuates MPP+-induced Neurotoxicity in SH-SY5Y Cells Via Regulation of Sirt1/Mn-SOD and GRP78/caspase-12 Pathways." International Journal of Molecular Sciences, vol. 15, no. 8, 2014, pp. 13209-22.
Yuan D, Wan JZ, Deng LL, et al. 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(8):13209-22.
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. (2014). Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways. International Journal of Molecular Sciences, 15(8), 13209-22. https://doi.org/10.3390/ijms150813209
Yuan D, et al. 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 Jul 28;15(8):13209-22. PubMed PMID: 25073091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways. AU - Yuan,Ding, AU - Wan,Jing-Zhi, AU - Deng,Li-Li, AU - Zhang,Chang-Cheng, AU - Dun,Yao-Yan, AU - Dai,Yan-Wen, AU - Zhou,Zhi-Yong, AU - Liu,Chao-Qi, AU - Wang,Ting, Y1 - 2014/07/28/ PY - 2014/04/20/received PY - 2014/06/05/revised PY - 2014/06/16/accepted PY - 2014/7/30/entrez PY - 2014/7/30/pubmed PY - 2015/3/31/medline SP - 13209 EP - 22 JF - International journal of molecular sciences JO - Int J Mol Sci VL - 15 IS - 8 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/25073091/Chikusetsu_saponin_V_attenuates_MPP+_induced_neurotoxicity_in_SH_SY5Y_cells_via_regulation_of_Sirt1/Mn_SOD_and_GRP78/caspase_12_pathways_ L2 - https://www.mdpi.com/resolver?pii=ijms150813209 DB - PRIME DP - Unbound Medicine ER -