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J Cell Mol Med. 2015 Jun;19(6):1333-45. doi: 10.1111/jcmm.12513. Epub 2015 Mar 17.

Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.

Author information

1
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Korea.
2
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, Korea.
3
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Kangneung, Korea.
4
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
5
Department of Biochemistry, School of Life Sciences & Biotechnology, Kyungpook National University, Taegu, Korea.

Abstract

Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage.

KEYWORDS:

Tat-Atox1; ischaemic injury; oxidative stress; protein therapy; protein transduction domain

PMID:
25781353
PMCID:
PMC4459847
DOI:
10.1111/jcmm.12513
[Indexed for MEDLINE]
Free PMC Article

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