IGF-1 protects intestinal epithelial cells from oxidative stress-induced apoptosis
IGF-1 protects intestinal epithelial cells from oxidative stress-induced apoptosis
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DOI：
10.1016/j.jss.2006.04.028
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发表时间：
2006-11-01
影响因子：
2.2
通讯作者：
Chung, Dai H.
中科院分区：
文献类型：
--
作者：
Baregamian, Naira;Song, Jun;Chung, Dai H.
背景活性氧（ROS）参与早产儿坏死性小肠结肠炎（NEC）的发病。我们最近发现，在ROS诱导的肠细胞凋亡过程中，多个细胞信号转导通路被激活;磷脂酰肌醇3-激酶（PI 3-K）通路在此过程中发挥抗凋亡作用。胰岛素样生长因子（IGF）-1激活PI 3-K通路以促进细胞存活;然而，IGF-1治疗在肠损伤期间的作用尚不清楚。本研究的目的是确定IGF-1是否保护肠细胞免受ROS诱导的凋亡。用IGF-1（100 nM）、过氧化氢（H2 O2; 500 μ M）或组合处理大鼠肠上皮（RIE）-1细胞。进行蛋白质印迹以评估Akt（PI 3-K的下游效应物）的磷酸化。进行细胞死亡检测ELISA、DCHF和JC-1测定以证明IGF-1的保护作用。用磷脂酰肌醇3-激酶（PI 3-K）抑制剂渥曼青霉素（Wortmannin）研究IGF-1的PI 3-K依赖性作用机制。H2 O2处理导致肠上皮细胞凋亡增加，细胞内ROS产生和线粒体膜去极化; IGF-1预处理减弱了这种反应，而不影响ROS的产生。IGF-1处理后，H2 O2诱导的Akt磷酸化水平进一步升高;渥曼青霉素可消除这些作用。在ROS诱导的肠上皮细胞损伤过程中，PI 3-K通路被激活; IGF-1通过PI 3-K激活在该反应期间发挥抗凋亡作用。更好地了解IGF-1介导的PI 3-K激活的确切作用可能有助于我们开发针对NEC的新疗法。(c)2006年爱思唯尔公司All rights reserved.
Background. Reactive oxygen species (ROS) are involved in the pathogenesis of necrotizing enterocolitis (NEC) in premature infants. We have recently found that activation of multiple cellular signaling transduction pathways occurs during ROS-induced intestinal cell apoptosis; the phosphatidylinositol 3-kinase (PI3-K) pathway plays an anti-apoptotic role during this process. Insulin-like growth factor (IGF)-1 activates PI3-K pathway to promote cell survival; however, the effects of IGF-1 treatment during gut injury are not clearly defined. The purpose of this study was to determine whether IGF-1 protects intestinal cells from ROS-induced apoptosis.Materials and methods. Rat intestinal epithelial (RIE)-1 cells were treated with either IGF-1 (100 nM), hydrogen peroxide (H2O2; 500 mu M), or combination. Western blotting was performed to assess phosphorylation of Akt, a downstream effector of PI3-K. Cell Death Detection ELISA, DCHF, and JC-1 assays were performed to demonstrate protective effects of IGF-1. Wortmannin, an inhibitor of PI3-K, was used to show PI3-K-dependent mechanism of action for IGF-1.Results. H2O2 treatment resulted in increased intestinal epithelial cell apoptosis with intracellular ROS generation and mitochondrial membrane depolarization; IGF-1 pre-treatment attenuated this response without affecting ROS production. H2O2-induced phosphorylation of Akt was further increased with IGF-1 treatment; wortmannin abolished these effects in RIE-1 cells.Conclusions. PI3-K pathway is activated during ROS-induced intestinal epithelial cell injury; IGF-1 exerted an anti-apoptotic effect during this response by PI3-K activation. A better understanding of the exact role of IGF-1-mediated activation of PI3-K may allow us to facilitate the development of novel therapy against NEC. (c) 2006 Elsevier Inc. All rights reserved.