Protective effect of GK2 fused BLVRA protein against oxidative stress-induced dopaminergic neuronal cell damage
- Authors
- Choi, Yeon Joo; Kwon, Hyun Jung; Shin, Min Jea; Kim, Dae Won; Youn, Gi Soo; Park, Jung Hwan; Yeo, Hyeon Ji; Yeo, Eun Ji; Kim, Hyeong Seop; Lee, Lee Re; Kim, Na Yeon; Kwon, Su Yeon; Kim, Duk-Soo; Kim, Gun Woo; Park, Jinseu; Han, Kyu Hyung; Lee, Keun Wook; Park, Jong Kook; Lee, Chan Hee; Eum, Won Sik; Choi, Soo Young
- Issue Date
- Jun-2023
- Publisher
- Blackwell Publishing Inc.
- Keywords
- GK2-BLVRA; MAPK; oxidative stress; Parkinson's disease; protein therapy
- Citation
- FEBS Journal, v.290, no.11, pp 2923 - 2938
- Pages
- 16
- Journal Title
- FEBS Journal
- Volume
- 290
- Number
- 11
- Start Page
- 2923
- End Page
- 2938
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/22169
- DOI
- 10.1111/febs.16721
- ISSN
- 1742-464X
1742-4658
- Abstract
- It is well known that oxidative stress is highly associated with Parkinson's disease (PD), and biliverdin reductase A (BLVRA) is known to have antioxidant properties against oxidative stress. In this study, we developed a novel N-acetylgalactosamine kinase (GK2) protein transduction domain (PTD) derived from adenosine A2A and fused with BLVRA to determine whether the GK2-BLVRA fusion protein could protect dopaminergic neuronal cells (SH-SY5Y) from oxidative stress in vitro and in vivo using a PD animal model. GK2-BLVRA was transduced into various cells, including SH-SY5Y cells, without cytotoxic effects, and this fusion protein protected SH-SY5Y cells and reduced reactive oxygen species production and DNA damage after 1-methyl-4-phenylpyridinium (MPP+) exposure. GK2-BLVRA suppressed mitogen-activated protein kinase (MAPK) activation and modulated apoptosis-related protein (Bcl-2, Bax, cleaved Caspase-3 and -9) expression levels. In the PD animal model, GK2-BLVRA transduced into the substantia nigra crossed the blood-brain barrier and markedly reduced dopaminergic neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced animals. These results indicate that our novel PTD GK-2 is useful for the transduction of protein, and GK2-BLVRA exhibits a beneficial effect against dopaminergic neuronal cell death in vitro and in vivo, suggesting that BLVRA can be used as a therapeutic agent for PD.
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Collections - College of Medicine > Department of Anatomy > 1. Journal Articles
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