Carbon monoxide (CO) inhibits hydrogen peroxide (H2O2)-induced oxidative stress and the activation of NF-κB signaling in lens epithelial cells
Carbon monoxide (CO) inhibits hydrogen peroxide (H2O2)-induced oxidative stress and the activation of NF-κB signaling in lens epithelial cells
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DOI：
10.1016/j.exer.2017.08.016
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发表时间：
2018-01-01
影响因子：
3.4
通讯作者：
Li, Zhaohui
中科院分区：
文献类型：
--
作者：
Huang, Yang;Ma, Tianju;Li, Zhaohui
晶状体上皮细胞（LECs）在晶状体的维持中起着至关重要的作用。先前，我们报道血红素加氧酶-1可以保护LECs免受过氧化氢（H2O2）诱导的凋亡和氧化应激；然而，据我们所知，这些保护机制尚未得到解释。由于一氧化碳（CO）是血红素降解的活性副产物，我们研究了h2o2处理的人LECs （SRA 01/04）和兔LECs的细胞保护机制。CO释放分子-3作为CO释放载体。Western blot和免疫荧光染色检测核因子κ B (nf - κ B) p65的核易位。此外，测定细胞内活性氧（ROS）、抗氧化剂和凋亡分子（Bax、Bcl-2和caspase-3）的水平。流式细胞术检测细胞凋亡率。我们的研究结果表明，低浓度的CO释放分子-3可以减弱NF-kappa B p65核易位，减少ROS的产生，并提高细胞内谷胱甘肽和超氧化物歧化酶的水平。此外，低浓度的CO抑制h2o2诱导的凋亡分子，从而减少LECs的凋亡。这些结果表明，低浓度的CO通过减弱NF-kappa B p65核易位，减少ROS和凋亡分子的产生，恢复抗氧化酶水平，从而抑制LECs凋亡，从而保护LECs免受h2o2诱导的氧化损伤。(C) 2017 Elsevier Ltd.版权所有。
Lens epithelial cells (LECs) play a critical role in the maintenance of clear crystalline lens. Previously, we reported that heme oxygenase-1 can protect LECs from hydrogen peroxide (H2O2) induced apoptosis and oxidative stress; however, to the best of our knowledge, these protection mechanisms have not yet been explained. As carbon monoxide (CO) is an active by-product of heme degradation, we investigated its cytoprotective mechanism in both H2O2-treated human LECs (SRA 01/04) and primary rabbit LECs. CO-releasing molecule-3 was used as a CO releasing vehicle. The nuclear translocation of nuclear factor kappa B (NF-kappa B) p65 was monitored by Western blot and immunofluorescence staining. In addition, the levels of intracellular reactive oxygen species (ROS), antioxidants, and apoptotic molecules (Bax, Bcl-2, and caspase-3) were measured. Furthermore, cell apoptosis rate was quantified by flow cytometry. Our results disclosed that low concentrations of CO released from CO-releasing molecule-3 can attenuate NF-kappa B p65 nuclear translocation, reduce ROS generation, and enhance intracellular glutathione and superoxide dismutase levels. Moreover, low concentrations of CO inhibited H2O2-induced apoptotic molecules, thereby decreasing the apoptosis of LECs. These findings suggest that low concentrations of CO protect LECs from H2O2-induced oxidative damage by attenuating NF-kappa B p65 nuclear translocation, reducing the generation of ROS and apoptotic molecules, and restoring antioxidant enzyme levels, thereby inhibiting LECs apoptosis. (C) 2017 Elsevier Ltd. All rights reserved.