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Mol Med Rep. 2018 Aug;18(2):2216-2228. doi: 10.3892/mmr.2018.9176. Epub 2018 Jun 15.

PEP‑1‑glutaredoxin 1 protects against hippocampal neuronal cell damage from oxidative stress via regulation of MAPK and apoptotic signaling pathways.

Author information

1
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 24252, Republic of South Korea.
2
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung‑Wonju National University, Gangneung, Gangwon 25457, Republic of South Korea.
3
Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan‑Si, South Chungcheong 31538, Republic of South Korea.
4
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Republic of South Korea.
5
Department of Neurosurgery, Hallym University Medical Center, Chuncheon, Gangwon 24253, Republic of South Korea.

Abstract

Oxidative stress is known to be a primary risk factor for neuronal diseases. Glutaredoxin (GLRX)‑1, a redox‑regulator of the thioredoxin superfamily, is known to exhibit an important role in cell survival via various cellular functions. However, the precise roles of GLRX1 in brain ischemia are still not fully understood. The present study investigated whether transduced PEP‑1‑GLRX1 protein has protective effects against oxidative stress in cells and in an animal model. Transduced PEP‑1‑GLRX1 protein increased HT‑22 cell viability under oxidative stress and this fusion protein significantly reduced intracellular reactive oxygen species and levels of DNA damage. In addition, PEP‑1‑GLRX1 protein regulated RAC‑a serine/threonine‑protein kinase and mitogen‑activated protein kinase signaling, in addition to apoptotic signaling including B cell lymphoma (Bcl)‑2, Bcl‑2 associated X, apoptosis regulator, pro‑caspase‑9 and p53 expression levels. In an ischemic animal model, it was verified that PEP‑1‑GLRX1 transduced into the Cornu Ammonis 1 region of the animal brain, where it markedly protected against ischemic injury. These results indicate that PEP‑1‑GLRX1 attenuates neuronal cell death resulting from oxidative stress in vitro and in vivo. Therefore, PEP‑1‑GLRX1 may exhibit a beneficial role in the treatment of neuronal disorders, including ischemic injury.

PMID:
29916538
DOI:
10.3892/mmr.2018.9176
[Indexed for MEDLINE]

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