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Free Radic Biol Med. 2014 Apr;69:181-96. doi: 10.1016/j.freeradbiomed.2014.01.006. Epub 2014 Jan 17.

Neuroprotective effects of PEP-1-carbonyl reductase 1 against oxidative-stress-induced ischemic neuronal cell damage.

Author information

1
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea.
2
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
3
Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chunchon 200-701, South Korea.
4
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea. Electronic address: vetmed2@snu.ac.kr.
5
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, South Korea. Electronic address: sychoi@hallym.ac.kr.

Abstract

Human carbonyl reductase 1 (CBR1) is a member of the NADPH-dependent short-chain dehydrogenase/reductase superfamily that is known to play an important role in neuronal cell survival via its antioxidant function. Oxidative stress is one of the major causes of degenerative disorders including ischemia. However, the role CBR1 plays with regard to ischemic injury is as yet poorly understood. Protein transduction domains such as PEP-1 are well known and now commonly used to deliver therapeutic proteins into cells. In this study, we prepared PEP-1-CBR1 protein and examined whether it protects against oxidative-stress-induced neuronal cell damage. PEP-1-CBR1 protein was efficiently transduced into hippocampal neuronal HT-22 cells and protected against hydrogen peroxide (H2O2)-induced neuronal cell death. Transduced PEP-1-CBR1 protein drastically inhibited H2O2-induced reactive oxygen species production, the oxidation of intracellular macromolecules, and the activation of mitogen-activated protein kinases, as well as cellular apoptosis. Furthermore, we demonstrated that transduced PEP-1-CBR1 protein markedly protected against neuronal cell death in the CA1 region of the hippocampus resulting from ischemic injury in an animal model. In addition, PEP-1-CBR1 protein drastically reduced activation of glial cells and lipid peroxidation in an animal model. These results indicate that PEP-1-CBR1 protein significantly protects against oxidative-stress-induced neuronal cell death in vitro and in vivo. Therefore, we suggest that PEP-1-CBR1 protein may be a therapeutic agent for the treatment of ischemic injuries as well as oxidative-stress-induced cell damage and death.

KEYWORDS:

Apoptosis; Free radicals; Ischemic injury; Oxidative stress; PEP-1–CBR1; Protein therapy

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