title: Tat-glyoxalase protein inhibits against ischemic neuronal cell damage and ameliorates ischemic injury.
abstract: Methylglyoxal (MG), a metabolite of glucose, is the major precursor of protein glycation and induces apoptosis. MG is associated with neurodegeneration, including oxidative stress and impaired glucose metabolism, and is efficiently metabolized to S-D-lactoylglutathione by glyoxalase (GLO). Although GLO has been implicated as being crucial in various diseases including ischemia, its detailed functions remain unclear. Therefore, we investigated the protective effect of GLO (GLO1 and GLO2) in neuronal cells and an animal ischemia model using Tat-GLO proteins. Purified Tat-GLO protein efficiently transduced into HT-22 neuronal cells and protected cells against MG- and H2O2-induced cell death, DNA fragmentation, and activation of caspase-3 and mitogen-activated protein kinase. In addition, transduced Tat-GLO protein increased D-lactate in MG- and H2O2-treated cells whereas glycation end products (AGE) and MG levels were significantly reduced in the same cells. Gerbils treated with Tat-GLO proteins displayed delayed neuronal cell death in the CA1 region of the hippocampus compared with a control. Furthermore, the combined neuroprotective effects of Tat-GLO1 and Tat-GLO2 proteins against ischemic damage were significantly higher than those of each individual protein. Those results demonstrate that transduced Tat-GLO protein protects neuronal cells by inhibiting MG- and H2O2-mediated cytotoxicity in vitro and in vivo. Therefore, we suggest that Tat-GLO proteins could be useful as a therapeutic agent for various human diseases related to oxidative stress including brain diseases.
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Min Jea
authors.initials: MJ
authors.lastname: Shin
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Yeom Pyo
authors.initials: YP
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Hyo Sang
authors.initials: HS
authors.lastname: Jo
authors.affiliation: Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-si 330-090, Korea.
authors.forename: Duk-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: School of Life Sciences, College of Natural Sciences, Kyungpook National University, Taegu 702-702, Republic of Korea.
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, Republic of Korea.
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.affiliation: Department of Neurosurgery, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, Republic of Korea.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. Electronic address: wseum@hallym.ac.kr.
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.affiliation: Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. Electronic address: sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D053938:DNA Fragmentation; D015870:Gene Expression; D015696:Gene Products, tat / Q000235:genetics / Q000378:metabolism; D005849:Gerbillinae; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007791:Lactoylglutathione Lyase / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013869:Thiolester Hydrolases / Q000235:genetics* / Q000378:metabolism; D000099301:Hydroxyacylglutathione Hydrolase
chemical_list: D053148:Caspase 3; D015696:Gene Products, tat; D017127:Glycation End Products, Advanced; D006861:Hydrogen Peroxide; D007791:Lactoylglutathione Lyase; D020928:Mitogen-Activated Protein Kinases; D011765:Pyruvaldehyde; D011993:Recombinant Fusion Proteins; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C505409:Casp3 protein, mouse
keywords: Glyoxalase (GLO); Ischemic damage; Methylglyoxal (MG); Oxidative stress; Protein therapy