PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model

Eun Hee Ahn, Dae Won Kim, Min Jea Shin, Young Nam Kim, Hye Ri Kim, Su Jung Woo, So Mi Kim, Duk Soo Kim, Joon Kim, Jinseu Park, Won Sik Eum, Hyun Sook Hwang, Soo Young Choi

Research output: Contribution to journalArticle

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Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by a gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Ribosomal protein S3 (rpS3) has multiple functions related to protein synthesis, antioxidative activity, and UV endonuclease III activity. We have previously shown that PEP-1-rpS3 inhibits skin inflammation and provides neuroprotection against experimental cerebral ischemic damage. In this study, we examined whether PEP-1-rpS3 can protect DA neurons against oxidative stress in SH-SY5Y neuroblastoma cells and in a 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-rpS3 was efficiently delivered to SH-SY5Y cells and the SN of the brain as confirmed by Western blot and immunohistochemical analysis. PEP-1-rpS3 significantly inhibited reactive oxygen species generation and DNA fragmentation induced by 1-methyl-4- phenylpyridinium, consequently leading to the survival of SH-SY5Y cells. The neuroprotection was related to the antiapoptotic activity of PEP-1-rpS3 that affected the levels of proapoptotic and antiapoptotic mediators. In addition, immunohistochemical data collected using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that PEP-1-rpS3 markedly protected DA cells in the SN against MPTP-induced oxidative stress. Therefore, our results suggest that PEP-1-rpS3 may be a potential therapy for PD.

Original languageEnglish
Pages (from-to)36-45
Number of pages10
JournalFree Radical Biology and Medicine
Volume55
DOIs
Publication statusPublished - 2013 Feb 1

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Dopaminergic Neurons
Neurons
Parkinson Disease
Substantia Nigra
Oxidative stress
Brain
Oxidative Stress
1-Methyl-4-phenylpyridinium
Neurodegenerative diseases
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Peptamen
ribosomal protein S3
4-phenyl-1,2,3,6-tetrahydropyridine
Tyrosine 3-Monooxygenase
DNA Fragmentation
Neuroblastoma
Neurodegenerative Diseases
Reactive Oxygen Species
Skin
Western Blotting

Keywords

  • Apoptosis
  • Free radicals
  • Oxidative stress
  • Parkinson's disease
  • Protein transduction domain
  • Ribosomal protein S3

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model. / Hee Ahn, Eun; Won Kim, Dae; Jea Shin, Min; Nam Kim, Young; Ri Kim, Hye; Jung Woo, Su; Mi Kim, So; Kim, Duk Soo; Kim, Joon; Park, Jinseu; Sik Eum, Won; Hwang, Hyun Sook; Choi, Soo Young.

In: Free Radical Biology and Medicine, Vol. 55, 01.02.2013, p. 36-45.

Research output: Contribution to journalArticle

Hee Ahn, E, Won Kim, D, Jea Shin, M, Nam Kim, Y, Ri Kim, H, Jung Woo, S, Mi Kim, S, Kim, DS, Kim, J, Park, J, Sik Eum, W, Hwang, HS & Choi, SY 2013, 'PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model', Free Radical Biology and Medicine, vol. 55, pp. 36-45. https://doi.org/10.1016/j.freeradbiomed.2012.11.008
Hee Ahn, Eun ; Won Kim, Dae ; Jea Shin, Min ; Nam Kim, Young ; Ri Kim, Hye ; Jung Woo, Su ; Mi Kim, So ; Kim, Duk Soo ; Kim, Joon ; Park, Jinseu ; Sik Eum, Won ; Hwang, Hyun Sook ; Choi, Soo Young. / PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model. In: Free Radical Biology and Medicine. 2013 ; Vol. 55. pp. 36-45.
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AU - Ri Kim, Hye

AU - Jung Woo, Su

AU - Mi Kim, So

AU - Kim, Duk Soo

AU - Kim, Joon

AU - Park, Jinseu

AU - Sik Eum, Won

AU - Hwang, Hyun Sook

AU - Choi, Soo Young

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AB - Parkinson's disease (PD) is a neurodegenerative disease characterized by a gradual loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Ribosomal protein S3 (rpS3) has multiple functions related to protein synthesis, antioxidative activity, and UV endonuclease III activity. We have previously shown that PEP-1-rpS3 inhibits skin inflammation and provides neuroprotection against experimental cerebral ischemic damage. In this study, we examined whether PEP-1-rpS3 can protect DA neurons against oxidative stress in SH-SY5Y neuroblastoma cells and in a 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced PD mouse model. PEP-1-rpS3 was efficiently delivered to SH-SY5Y cells and the SN of the brain as confirmed by Western blot and immunohistochemical analysis. PEP-1-rpS3 significantly inhibited reactive oxygen species generation and DNA fragmentation induced by 1-methyl-4- phenylpyridinium, consequently leading to the survival of SH-SY5Y cells. The neuroprotection was related to the antiapoptotic activity of PEP-1-rpS3 that affected the levels of proapoptotic and antiapoptotic mediators. In addition, immunohistochemical data collected using a tyrosine hydroxylase antibody and cresyl violet staining demonstrated that PEP-1-rpS3 markedly protected DA cells in the SN against MPTP-induced oxidative stress. Therefore, our results suggest that PEP-1-rpS3 may be a potential therapy for PD.

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