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Free Radic Biol Med. 2014 Feb;67:195-210. doi: 10.1016/j.freeradbiomed.2013.10.815. Epub 2013 Nov 16.

Tat-glyoxalase protein inhibits against ischemic neuronal cell damage and ameliorates ischemic injury.

Author information

1
Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
2
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 210-702, Korea.
3
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-si 330-090, Korea.
4
School of Life Sciences, College of Natural Sciences, Kyungpook National University, Taegu 702-702, Republic of Korea.
5
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, Republic of Korea.
6
Department of Neurosurgery, College of Medicine, Hallym University, Chunchon, Kangwon-Do 200-702, Republic of Korea.
7
Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. Electronic address: wseum@hallym.ac.kr.
8
Department of Biomedical Sciences and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea. Electronic address: sychoi@hallym.ac.kr.

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.

KEYWORDS:

Glyoxalase (GLO); Ischemic damage; Methylglyoxal (MG); Oxidative stress; Protein therapy

[Indexed for MEDLINE]

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