Molecular Neurobiology

, Volume 52, Issue 1, pp 422–431 | Cite as

PRDX6 Exacerbates Dopaminergic Neurodegeneration in a MPTP Mouse Model of Parkinson’s Disease

  • Hyung-Mun Yun
  • Dong Young Choi
  • Ki Wan Oh
  • Jin Tae Hong
Article
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Abstract

Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase (GPx) and calcium-independent phospholipase A2 (iPLA2) activities. Expression of PRDX6 has been detected in human Parkinson’s disease (PD) and dementia patients. However, no study has described PRDX6 function in the dopaminergic neurodegeneration in PD. Herein, we investigated the effects of PRDX6 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration using PRDX6 transgenic (Tg) mice. Immunohistochemistry (IHC) and Western blot data for tyrosine hydroxylase (TH) showed that PRDX6 Tg mice had much higher loss of dopaminergic neurons by MPTP administration compared to non-Tg mice, as well as there was much higher behavioral impairment and astrocyte activation in PRDX6 Tg mice. MPTP-induced GPx activity was not different between PRDX6 Tg mice and non-Tg mice, which is accompanied by hyperoxidation of PRDX6. While iPLA2 activity was increased in PRDX6 Tg mice followed by an increase in the level of ROS and 4-hydroxynonenal (4-HNE). Intriguingly, the expression pattern of PRDX6 showed similar distribution and co-localization with astrocytes, but not neuron in the mouse and human brain. Furthermore, we demonstrated that iPLA2 activity of PRDX6 induced astrocytic activation followed by increased proinflammatory cytokines (TNF-α and IL1-β), 4-HNE, and PRDX6 hyperoxidation in primary cultured astrocytes. Our findings provide novel insights for PRDX6 function on nigrostriatal dopaminergic neuronal system, and we suggest that PRDX6 has an important role in dopaminergic neurodegeneration of PD.

Keywords

PRDX6 iPLA2 4-HNE MPTP Parkinson’s disease 
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Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MISP) (No. MRC, 2008-0062275), by a grant (A101836) from the Korean Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea. We extend our appreciation to Dr. Sanghyeon Kim (Associate Director for database management, SMRI Laboratory of Brain Research, Rockville, MD) for kindly providing the human brain test samples.

Conflict of Interest

The authors declare no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Hyung-Mun Yun
    • 1
  • Dong Young Choi
    • 2
  • Ki Wan Oh
    • 1
  • Jin Tae Hong
    • 1
  1. 1.College of Pharmacy and Medical Research CenterChungbuk National UniversityCheongjuRepublic of Korea
  2. 2.College of PharmacyYeungnam UniversityGyeongsanRepublic of Korea

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