Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling

• Main Authors: Sang Jin Kim, Min Jea Shin, Dae Won Kim, Hyeon Ji Yeo, Eun Ji Yeo, Yeon Joo Choi, Eun Jeong Sohn, Kyu Hyung Han, Jinseu Park, Keun Wook Lee, Jong Kook Park, Yong-Jun Cho, Duk-Soo Kim, Won Sik Eum, Soo Young Choi
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: International Journal of Molecular Sciences
• Subjects: Tat-BLVRA; oxidative stress; MAPK; ischemic injury; protein therapy
• Online Access: https://www.mdpi.com/1422-0067/21/8/2672
• ISSN: 1661-6596; 1422-0067

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. 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 animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H₂O₂-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.