Korea Zoonoses Research Institute, Bio-Safety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
Int J Mol Med. 2012 Nov;30(5):1069-74. doi: 10.3892/ijmm.2012.1087. Epub 2012 Aug 8.
Insulin-like growth factor-1 (IGF-1) is one of the most important components of bovine colostrum. It exhibits antiapoptotic and antioxidative activities. Prion diseases are neurodegenerative disorders caused by cell death through mitochondrial dysfunction and increasing generation of reactive oxygen species (ROS). This study examined the protective effect of IGF-1 on residues 106-126 of the cellular prion protein [PrP (106-126)]-mediated mitochondrial neurotoxicity and oxidative stress. In SH-SY5Y human neuronal cells, treatment with PrP (106-126) decreased the cell viability and IGF-1 pretreatment markedly blocked the PrP (106-126)-induced neuronal cell death. IGF-1 inhibited PrP (106-126)-induced intracellular ROS generation and mitochondrial oxidative stress. In addition, IGF-1 blocked the translocation of the Bax protein to the mitochondria induced by PrP (106-126). These results demonstrate that IGF-1 protects neuronal cells against PrP (106-126)-mediated neurotoxicity through an antioxidative effect and blockage of mitochondrial Bax translocation. The results also suggest that regulation of IGF-1 secretion may have a therapeutic potential in the management of mitochondrial dysfunction and oxidative stress-induced neurodegeneration.
胰岛素样生长因子-1（IGF-1）是牛初乳中最重要的成分之一。它具有抗细胞凋亡和抗氧化作用。朊病毒病是由线粒体功能障碍和活性氧（ROS）生成增加导致的神经退行性疾病。本研究探讨了 IGF-1 对细胞朊蛋白 [PrP（106-126）] 介导的线粒体神经毒性和氧化应激的保护作用。在 SH-SY5Y 人神经元细胞中，用 PrP（106-126）处理会降低细胞活力，而 IGF-1 预处理则明显阻断了 PrP（106-126）诱导的神经元细胞死亡。IGF-1 抑制 PrP（106-126）诱导的细胞内 ROS 生成和线粒体氧化应激。此外，IGF-1 阻断了 PrP（106-126）诱导的 Bax 蛋白向线粒体的易位。这些结果表明，IGF-1 通过抗氧化作用和阻断线粒体 Bax 易位来保护神经元细胞免受 PrP（106-126）介导的神经毒性。研究结果还表明，调节 IGF-1 的分泌可能具有治疗线粒体功能障碍和氧化应激诱导的神经退行性变的潜力。
