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

24 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+)-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

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model'. Together they form a unique fingerprint.

  • Cite this

    Kim, M. J., Park, M., Kim, D. W., Shin, M. J., Son, O., Jo, H. S., Yeo, H. J., Cho, S. B., Park, J. H., Lee, C. H., Kim, D. S., Kwon, O. S., Kim, J., Han, K. H., Park, J., Eum, W. S., & Choi, S. Y. (2015). Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model. Biomaterials, 64, 45-56. https://doi.org/10.1016/j.biomaterials.2015.06.015