Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, College of Medicine, Hallym University, Chunchon 200-702, Korea.
Free Radic Biol Med. 2009 Oct 1;47(7):941-52. doi: 10.1016/j.freeradbiomed.2009.06.036. Epub 2009 Jul 3.
Antioxidant enzymes are considered to have beneficial effects against various diseases mediated by reactive oxygen species (ROS). Ischemia is characterized by both oxidative stress and changes in the antioxidant defense system. Catalase (CAT) and superoxide dismutase (SOD) are major antioxidant enzymes by which cells counteract the deleterious effects of ROS. To investigate the protective effects of CAT, we constructed PEP-1-CAT cell-permeative expression vectors. When PEP-1-CAT fusion proteins were added to the culture medium of neuronal cells, they rapidly entered the cells and protected them against oxidative stress-induced neuronal cell death. Immunohistochemical analysis revealed that PEP-1-CAT prevented neuronal cell death in the hippocampus induced by transient forebrain ischemia. Moreover, we showed that the protective effect of PEP-1-CAT was observed in neuronal cells treated with PEP-1-SOD. Therefore, we suggest that transduced PEP-1-CAT and PEP-1-SOD fusion proteins could be useful as therapeutic agents for various human diseases related to oxidative stress, including stroke.
抗氧化酶被认为对活性氧(ROS)介导的各种疾病具有有益的影响。缺血的特征是氧化应激和抗氧化防御系统的变化。过氧化氢酶(CAT)和超氧化物歧化酶(SOD)是细胞对抗 ROS 有害影响的主要抗氧化酶。为了研究 CAT 的保护作用,我们构建了 PEP-1-CAT 细胞通透性表达载体。当 PEP-1-CAT 融合蛋白添加到神经元细胞的培养基中时,它们迅速进入细胞并保护它们免受氧化应激诱导的神经元细胞死亡。免疫组织化学分析显示,PEP-1-CAT 可防止短暂性前脑缺血诱导的海马神经元细胞死亡。此外,我们表明 PEP-1-CAT 在接受 PEP-1-SOD 处理的神经元细胞中观察到保护作用。因此,我们建议转导的 PEP-1-CAT 和 PEP-1-SOD 融合蛋白可作为与氧化应激相关的各种人类疾病(包括中风)的治疗剂。