Department of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea.
Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, Korea.
Int J Mol Sci. 2020 Apr 11;21(8):2672. doi: 10.3390/ijms21082672.
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 HO-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.
活性氧（ROS）是包括缺血在内的神经元疾病的主要危险因素。虽然胆红素还原酶 A（BLVRA）通过其抗氧化功能在细胞存活中发挥关键作用，但它在海马神经元（HT-22）细胞和动物缺血性损伤中的作用尚不清楚。在这项研究中，研究了可诱导融合蛋白 Tat-BLVRA 对 HO 诱导的 HT-22 细胞死亡和动物缺血模型的影响。转导的 Tat-BLVRA 明显抑制细胞死亡、DNA 片段化和 ROS 的产生。转导的 Tat-BLVRA 抑制细胞凋亡和丝裂原激活蛋白激酶（MAPK）信号通路，它可以穿过血脑屏障（BBB），并显著防止缺血模型中海马细胞死亡。这些结果表明 Tat-BLVRA 为缺血提供了一种治疗分子的可能性。
