title: Tat-HSP22 inhibits oxidative stress-induced hippocampal neuronal cell death by regulation of the mitochondrial pathway.
abstract: Oxidative stress plays an important role in the progression of various neuronal diseases including ischemia. Heat shock protein 22 (HSP22) is known to protect cells against oxidative stress. However, the protective effects and mechanisms of HSP22 in hippocampal neuronal cells under oxidative stress remain unknown. In this study, we determined whether HSP22 protects against hydrogen peroxide (H2O2)-induced oxidative stress in HT-22 using Tat-HSP22 fusion protein. We found that Tat-HSP22 transduced into HT-22 cells and that H2O2-induced cell death, oxidative stress, and DNA damage were significantly reduced by Tat-HSP22. In addition, Tat-HSP22 markedly inhibited H2O2-induced mitochondrial membrane potential, cytochrome c release, cleaved caspase-3, and Bax expression levels, while Bcl-2 expression levels were increased in HT-22 cells. Further, we showed that Tat-HSP22 transduced into animal brain and inhibited cleaved-caspase-3 expression levels as well as significantly inhibited hippocampal neuronal cell death in the CA1 region of animals in the ischemic animal model. In the present study, we demonstrated that transduced Tat-HSP22 attenuates oxidative stress-induced hippocampal neuronal cell death through the mitochondrial signaling pathway and plays a crucial role in inhibiting neuronal cell death, suggesting that Tat-HSP22 protein may be used to prevent oxidative stress-related brain diseases including ischemia.
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Su Bin
authors.initials: SB
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Chi Hern
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Yeo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Hyeon Ji
authors.initials: HJ
authors.lastname: Yeo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Sohn
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Ora
authors.initials: O
authors.lastname: Son
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, Korea.
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, 31538, Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si, 31538, Korea.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Yu
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Keun Wook
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea. wseum@hallym.ac.kr.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, Korea. sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D015696:Gene Products, tat / Q000494:pharmacology*; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006624:Hippocampus / Q000473:pathology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017346:Protein Serine-Threonine Kinases / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014161:Transduction, Genetic
chemical_list: D015696:Gene Products, tat; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases
keywords: Apoptosis; Ischemia; Oxidative stress; Protein therapy; Tat-HSP22