Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model

Mi Jin Kim, Meeyoung Park, Dae Won Kim, Min Jea Shin, Ora Son, Hyo Sang Jo, Hyeon Ji Yeo, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Duk Soo Kim, Oh Shin Kwon, Joon Kim, Kyu Hyung Han, Jinseu Park, Won Sik Eum, Soo Young Choi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>)-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases.

Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalBiomaterials
Volume64
DOIs
Publication statusPublished - 2015 Sep 1

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Aryldialkylphosphatase
Parkinson Disease
Oxidative stress
Chemical activation
Proteins
Oxidative Stress
Lipoproteins
Matrix Metalloproteinase 9
1-Methyl-4-phenylpyridinium
Phospholipids
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cell death
Substantia Nigra
HDL Lipoproteins
Mesencephalon
Peptamen
Neurodegenerative Diseases
Fusion reactions
Lipopolysaccharides
Tissue

Keywords

  • Dopaminergic neuronal death
  • Inflammation
  • Oxidative stress
  • Parkinson's disease
  • PEP-1-PON1
  • Protein therapy

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model. / Kim, Mi Jin; Park, Meeyoung; Kim, Dae Won; Shin, Min Jea; Son, Ora; Jo, Hyo Sang; Yeo, Hyeon Ji; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Kim, Duk Soo; Kwon, Oh Shin; Kim, Joon; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young.

In: Biomaterials, Vol. 64, 01.09.2015, p. 45-56.

Research output: Contribution to journalArticle

Kim, MJ, Park, M, Kim, DW, Shin, MJ, Son, O, Jo, HS, Yeo, HJ, Cho, SB, Park, JH, Lee, CH, Kim, DS, Kwon, OS, Kim, J, Han, KH, Park, J, Eum, WS & Choi, SY 2015, 'Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model', Biomaterials, vol. 64, pp. 45-56. https://doi.org/10.1016/j.biomaterials.2015.06.015
Kim, Mi Jin ; Park, Meeyoung ; Kim, Dae Won ; Shin, Min Jea ; Son, Ora ; Jo, Hyo Sang ; Yeo, Hyeon Ji ; Cho, Su Bin ; Park, Jung Hwan ; Lee, Chi Hern ; Kim, Duk Soo ; Kwon, Oh Shin ; Kim, Joon ; Han, Kyu Hyung ; Park, Jinseu ; Eum, Won Sik ; Choi, Soo Young. / Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model. In: Biomaterials. 2015 ; Vol. 64. pp. 45-56.
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abstract = "Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases.",
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AU - Kim, Mi Jin

AU - Park, Meeyoung

AU - Kim, Dae Won

AU - Shin, Min Jea

AU - Son, Ora

AU - Jo, Hyo Sang

AU - Yeo, Hyeon Ji

AU - Cho, Su Bin

AU - Park, Jung Hwan

AU - Lee, Chi Hern

AU - Kim, Duk Soo

AU - Kwon, Oh Shin

AU - Kim, Joon

AU - Han, Kyu Hyung

AU - Park, Jinseu

AU - Eum, Won Sik

AU - Choi, Soo Young

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases.

AB - Parkinson's disease (PD) is an oxidative stress-mediated neurodegenerative disorder caused by selective dopaminergic neuronal death in the midbrain substantia nigra. Paraoxonase 1 (PON1) is a potent inhibitor of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) against oxidation by destroying biologically active phospholipids with potential protective effects against oxidative stress-induced inflammatory disorders. In a previous study, we constructed protein transduction domain (PTD) fusion PEP-1-PON1 protein to transduce PON1 into cells and tissue. In this study, we examined the role of transduced PEP-1-PON1 protein in repressing oxidative stress-mediated inflammatory response in microglial BV2 cells after exposure to lipopolysaccharide (LPS). Moreover, we identified the functions of transduced PEP-1-PON1 proteins which include, mitigating mitochondrial damage, decreasing reactive oxidative species (ROS) production, matrix metalloproteinase-9 (MMP-9) expression and protecting against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cells. Furthermore, transduced PEP-1-PON1 protein reduced MMP-9 expression and protected against dopaminergic neuronal cell death in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model. Taken together, these results suggest a promising therapeutic application of PEP-1-PON1 proteins against PD and other inflammation and oxidative stress-related neuronal diseases.

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KW - Inflammation

KW - Oxidative stress

KW - Parkinson's disease

KW - PEP-1-PON1

KW - Protein therapy

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