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Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways.
Int J Mol Sci. 2017 Dec 19; 18(12)IJ

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP⁺)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP⁺-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP⁺-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP⁺. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP⁺. Taken together, these results suggest that sulfuretin significantly attenuates MPP⁺-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD.

Authors+Show Affiliations

Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. ume.ramesh@gmail.com. Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea. ume.ramesh@gmail.com.Deptartment of Oriental Pharmacy, & Wonkwang-Oriental Medicines Research Institute, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. clickrama@gmail.com.Deptartment of Oriental Pharmacy, & Wonkwang-Oriental Medicines Research Institute, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. hyun104@wku.ac.kr.Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. sungykim@wku.ac.kr.Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea. jwseo@wku.ac.kr. Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Korea. jwseo@wku.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29257079

Citation

Pariyar, Ramesh, et al. "Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity Through Akt/GSK3β and ERK Signaling Pathways." International Journal of Molecular Sciences, vol. 18, no. 12, 2017.
Pariyar R, Lamichhane R, Jung HJ, et al. Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways. Int J Mol Sci. 2017;18(12).
Pariyar, R., Lamichhane, R., Jung, H. J., Kim, S. Y., & Seo, J. (2017). Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways. International Journal of Molecular Sciences, 18(12). https://doi.org/10.3390/ijms18122753
Pariyar R, et al. Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity Through Akt/GSK3β and ERK Signaling Pathways. Int J Mol Sci. 2017 Dec 19;18(12) PubMed PMID: 29257079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfuretin Attenuates MPP⁺-Induced Neurotoxicity through Akt/GSK3β and ERK Signaling Pathways. AU - Pariyar,Ramesh, AU - Lamichhane,Ramakanta, AU - Jung,Hyun Ju, AU - Kim,Sung Yeon, AU - Seo,Jungwon, Y1 - 2017/12/19/ PY - 2017/10/11/received PY - 2017/12/09/revised PY - 2017/12/11/accepted PY - 2017/12/20/entrez PY - 2017/12/20/pubmed PY - 2018/7/18/medline KW - Akt KW - ERK KW - GSK3β KW - MPP+ KW - Parkinson’s disease KW - apoptosis KW - p53 KW - sulfuretin JF - International journal of molecular sciences JO - Int J Mol Sci VL - 18 IS - 12 N2 - Parkinson's disease (PD) is the second most common neurodegenerative disease. It is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress and mitochondrial dysfunction contribute to the loss of dopaminergic neurons in PD. Sulfuretin is a potent antioxidant that is reported to be beneficial in the treatment of neurodegenerative diseases. In this study, we examined the protective effect of sulfuretin against 1-methyl-4-phenyl pyridinium (MPP⁺)-induced cell model of PD in SH-SY5Y cells and the underlying molecular mechanisms. Sulfuretin significantly decreased MPP⁺-induced apoptotic cell death, accompanied by a reduction in caspase 3 activity and polyADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated MPP⁺-induced production of intracellular reactive oxygen species (ROS) and disruption of mitochondrial membrane potential (MMP). Consistently, sulfuretin decreased p53 expression and the Bax/Bcl-2 ratio. Moreover, sulfuretin significantly increased the phosphorylation of Akt, GSK3β, and ERK. Pharmacological inhibitors of PI3K/Akt and ERK abolished the cytoprotective effects of sulfuretin against MPP⁺. An inhibitor of GSK3β mimicked sulfuretin-induced protection against MPP⁺. Taken together, these results suggest that sulfuretin significantly attenuates MPP⁺-induced neurotoxicity through Akt/GSK3β and ERK signaling pathways in SH-SY5Y cells. Our findings suggest that sulfuretin might be one of the potential candidates for the treatment of PD. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/29257079/Sulfuretin_Attenuates_MPP⁺_Induced_Neurotoxicity_through_Akt/GSK3β_and_ERK_Signaling_Pathways_ L2 - https://www.mdpi.com/resolver?pii=ijms18122753 DB - PRIME DP - Unbound Medicine ER -