The Texas Heart Institute and Center for Cardiovascular and Atherosclerosis Research, Department of Internal Medicine, University of Texas Medical School at Houston, TX 77030, USA.
Biochem Biophys Res Commun. 2012 Oct 5;426(4):615-9. doi: 10.1016/j.bbrc.2012.08.139. Epub 2012 Sep 6.
Oxidative stress contributes to tissue injury and cell death during the development of various diseases. The present study aims at investigating whether oxidative stress triggered by the exposure to hydrogen peroxide (H(2)O(2)) can induce apoptosis of induced pluripotent stem cells (iPS cells) in a mechanism mediated by insulin-like growth factor (IGF-1) and microRNA-1 (miR-1). iPS cells treated with H(2)O(2) showed increases in miR-1 expression, mitochondria dysfunction, cytochrome-c release and apoptosis, Addition of IGF-1 into the iPS cell cultures reduced the H(2)O(2) cytotoxicity. Prediction algorithms showed that 3'-untranslated regions of IGF-1 gene as a target of miR-1. Moreover, miR-1 mimic, but not miR-1 mimic negative control, diminished the protective effect of IGF-1 on H(2)O(2)-induced mitochondrial dysfunction, cytochrome-c release and apoptosis in iPS cells. In conclusion, IGF-1 inhibits H(2)O(2)-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. IGF-1's effect is, at least partially, regulated by miR-1 in iPS cells.
氧化应激在多种疾病的发展过程中导致组织损伤和细胞死亡。本研究旨在探讨氧化应激是否可以通过胰岛素样生长因子（IGF-1）和 microRNA-1（miR-1）介导的机制诱导诱导多能干细胞（iPS 细胞）凋亡。用 H（2）O（2）处理的 iPS 细胞表现出 miR-1 表达增加、线粒体功能障碍、细胞色素 c 释放和细胞凋亡。将 IGF-1 添加到 iPS 细胞培养物中可降低 H（2）O（2）的细胞毒性。预测算法表明，IGF-1 基因的 3'-非翻译区是 miR-1 的靶标。此外，miR-1 模拟物而非 miR-1 模拟物阴性对照可减弱 IGF-1 对 H（2）O（2）诱导的 iPS 细胞中线粒体功能障碍、细胞色素 c 释放和凋亡的保护作用。总之，IGF-1 抑制 H（2）O（2）诱导的线粒体功能障碍、细胞色素 c 释放和凋亡。IGF-1 在 iPS 细胞中的作用至少部分受 miR-1 调节。
