Page 8 - Q. Neuroscience

[Q. Neuroscience-5]

Tat-Biliverdin reductase A exerts a protective role in oxidative

stress-induced hippocampal neuronal cell damage by

regulating the apoptosis and MAPK signaling

Hyeon Ji Yeo¹, Sang Jin Kim¹, Eun Ji Yeo¹, Yeon Joo Choi¹, Min Jea Shin¹, Dae Won Kim², Eun Jeong

Sohn¹, Kyu Hyung Han¹, Jinseu Park¹, Keun Wook Lee¹, Jong Kook Park¹, Yong-Jun Cho³, Duk-Soo Kim⁴,

Won Sik Eum¹, Soo Young Choi¹

¹Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University,
Chuncheon 24252, Korea, ²Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences,

College of De, Gangneung-Wonju National University, Gangneung 25457, Korea, ³Department of Neurosurgery,
Hallym University Medical Center, Chuncheon 24253, Korea, ⁴Department of Anatomy, College of Medicine,

Soonchunhyang University, Cheonan-Si 31538, Korea

Reactive oxygen species (ROS) is known as one of major risk factors in various neuronal diseases including ischemic
insults. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its

role in hippocampal neuronal (HT-22) cells and ischemic animal model is not clearly understood yet. In this study,
we examined the effects of Tat-BLVRA on H2O2-induced HT-22 cell death and in an animal ischemia model. We

showed that Tat-BLVRA transduced into HT-22 cells and it markedly inhibited H2O2-induced HT-22 cell death and
decreased ROS levels. Also, transduced Tat-BLVRA inhibited the apoptosis and MAPK signaling pathway in H2O2

exposed HT-22 cells. In an ischemic animal model, transduced Tat-BLVRA passed through the blood-brain barrier
and this transduced protein significantly inhibited hippocampal neuronal cell death. These results demonstrated

that transduced Tat-BLVRA markedly protects against oxidative stress-induced hippocampal neuronal cell damage,
suggesting that Tat-BLVRA has a possibility as a therapeutic agent for oxidative stress-induced neuronal diseases

including ischemia.