Protective effects of cell permeable Tat-PIM2 protein on oxidative stress induced dopaminergic neuronal cell death
Min Jea Shin,
Won Sik Eum,
Gi Soo Youn,
Jung Hwan Park,
Hyeon Ji Yeo,
Eun Ji Yeo,
Hyun Jung Kwon,
Eun Jeong Sohn,
Lee Re Lee,
Na Yeon Kim,
Su Yeon Kwon,
Su Min Kim,
Hyo Young Jung,
Duk-Soo Kim,
Sung-Woo Cho,
Oh-Shin Kwon,
Dae Won Kim,
Soo Young Choi
Affiliations
Min Jea Shin
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Won Sik Eum
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Gi Soo Youn
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Jung Hwan Park
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Hyeon Ji Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Eun Ji Yeo
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Hyun Jung Kwon
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Eun Jeong Sohn
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Lee Re Lee
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Na Yeon Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Su Yeon Kwon
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Su Min Kim
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea
Hyo Young Jung
Department of Veterinary Medicine & Institute of Veterinary Science, Chungnam National University, Daejeon, 34134, South Korea
Duk-Soo Kim
Department of Anatomy and BK21 FOUR Project, College of Medicine, Soonchunhyang University, Cheonan-si 31538, South Korea
Sung-Woo Cho
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, South Korea
Oh-Shin Kwon
School of Life Sciences, College of Natural Sciences Kyungpook National University, Taegu 41566, South Korea
Dae Won Kim
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, South Korea; Corresponding author.
Soo Young Choi
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea; Corresponding author.
Background: Oxidative stress is considered as one of the main causes of Parkinson's disease (PD), however the exact etiology of PD is still unknown. Although it is known that Proviral Integration Moloney-2 (PIM2) promotes cell survival by its ability to inhibit formation of reactive oxygen species (ROS) in the brain, the precise functional role of PIM2 in PD has not been fully studied yet. Objective: We investigated the protective effect of PIM2 against apoptosis of dopaminergic neuronal cells caused by oxidative stress-induced ROS damage by using the cell permeable Tat-PIM2 fusion protein in vitro and in vivo. Methods: Transduction of Tat-PIM2 into SH-SY5Y cells and apoptotic signaling pathways were determined by Western blot analysis. Intracellular ROS production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. PD animal model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and protective effects were examined using immunohistochemistry. Results: Transduced Tat-PIM2 inhibited the apoptotic caspase signaling and reduced the production of ROS induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Furthermore, we confirmed that Tat-PIM2 transduced into the substantia nigra (SN) region through the blood-brain barrier and this protein protected the Tyrosine hydroxylase-positive cells by observation of immunohistostaining. Tat-PIM2 also regulated antioxidant biomolecules such as SOD1, catalase, 4-HNE, and 8-OHdG which reduce the formation of ROS in the MPTP-induced PD mouse model. Conclusion: These results indicated that Tat-PIM2 markedly inhibited the loss of dopaminergic neurons by reducing ROS damage, suggesting that Tat-PIM2 might be a suitable therapeutic agent for PD.
