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The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells.
J Cell Biochem. 2016 Apr; 117(4):917-26.JC

Abstract

Parkinson's disease (PD) is a common chronic neurodegenerative disorder associated with aging that primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SN). Retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells (SH-SY5Y+RA) have been broadly utilized in studies of mechanisms of the pathogenesis underlying 1-Methyl-4-phenyl pyridinium (MPP(+))-induced PD models. Here, we investigated the neuroprotective mechanisms of insulin on MPP(+)-induced neurotoxicity on SH-SY5Y+RA cells. Recent studies suggest that insulin has a protective effect against oxidative stress but not been elucidated for PD. In this study, pretreatment of insulin prevented the cell death in a dose dependent manner and lowered nitric oxide (NO) release, reactive oxygen species (ROS), and calcium ion (Ca(2+)) influx induced by MPP(+). Insulin also elevated tyrosine hydroxylase (TH) and insulin signaling pathways in dopaminergic neuron through activating PI3K/Akt/GSK-3 survival pathways which in turn inhibits MPP(+)-induced iNOS and ERK activation, and Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on MPP(+)-neurotoxicity in SH-SY5Y+RA cells.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Ramalingam M
Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.
Kim SJ
Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University, Seoul, Republic of Korea.

MeSH

1-Methyl-4-phenylpyridiniumCalciumCell DifferentiationCell Line, TumorCytotoxinsDopaminergic NeuronsGene Expression RegulationGlycogen Synthase Kinase 3HumansInsulinMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Neuroprotective AgentsNitric OxideNitric Oxide Synthase Type IIPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-bcl-2Reactive Oxygen SpeciesSignal TransductionTretinoinTyrosine 3-Monooxygenasebcl-2-Associated X Protein

Pub Type(s)

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

Language

eng

PubMed ID

26364587

Citation

Ramalingam, Mahesh, and Sung-Jin Kim. "The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells." Journal of Cellular Biochemistry, vol. 117, no. 4, 2016, pp. 917-26.
Ramalingam M, Kim SJ. The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells. J Cell Biochem. 2016;117(4):917-26.
Ramalingam, M., & Kim, S. J. (2016). The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells. Journal of Cellular Biochemistry, 117(4), 917-26. https://doi.org/10.1002/jcb.25376
Ramalingam M, Kim SJ. The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells. J Cell Biochem. 2016;117(4):917-26. PubMed PMID: 26364587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Neuroprotective Role of Insulin Against MPP(+) -Induced Parkinson's Disease in Differentiated SH-SY5Y Cells. AU - Ramalingam,Mahesh, AU - Kim,Sung-Jin, Y1 - 2015/09/30/ PY - 2015/06/22/received PY - 2015/09/10/accepted PY - 2015/9/15/entrez PY - 2015/9/15/pubmed PY - 2016/10/27/medline KW - Bcl-2 KW - GLYCOGEN SYNTHASE KINASE-3 (GSK-3) KW - INSULIN KW - PROTEIN KINASE B (Akt) KW - SH-SY5Y KW - TYROSINE HYDROXYLASE (TH) SP - 917 EP - 26 JF - Journal of cellular biochemistry JO - J Cell Biochem VL - 117 IS - 4 N2 - Parkinson's disease (PD) is a common chronic neurodegenerative disorder associated with aging that primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SN). Retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells (SH-SY5Y+RA) have been broadly utilized in studies of mechanisms of the pathogenesis underlying 1-Methyl-4-phenyl pyridinium (MPP(+))-induced PD models. Here, we investigated the neuroprotective mechanisms of insulin on MPP(+)-induced neurotoxicity on SH-SY5Y+RA cells. Recent studies suggest that insulin has a protective effect against oxidative stress but not been elucidated for PD. In this study, pretreatment of insulin prevented the cell death in a dose dependent manner and lowered nitric oxide (NO) release, reactive oxygen species (ROS), and calcium ion (Ca(2+)) influx induced by MPP(+). Insulin also elevated tyrosine hydroxylase (TH) and insulin signaling pathways in dopaminergic neuron through activating PI3K/Akt/GSK-3 survival pathways which in turn inhibits MPP(+)-induced iNOS and ERK activation, and Bax to Bcl-2 ratio. These results suggest that insulin has a protective effect on MPP(+)-neurotoxicity in SH-SY5Y+RA cells. SN - 1097-4644 UR - https://www.unboundmedicine.com/medline/citation/26364587/The_Neuroprotective_Role_of_Insulin_Against_MPP_+___Induced_Parkinson's_Disease_in_Differentiated_SH_SY5Y_Cells_ DB - PRIME DP - Unbound Medicine ER -