Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells
Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells
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DOI：
10.1016/j.exer.2007.09.010
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
van Kuijk, Frederik J. G. M.
中科院分区：
文献类型：
--
作者：
Kalariya, Nilesh M.;Ramana, Kota V.;van Kuijk, Frederik J. G. M.
类胡萝卜素已被认为是治疗年龄相关性黄斑变性（AMD）的潜在药物。在眼组织中，类胡萝卜素可经历氧化并形成类胡萝卜素衍生的醛（CDA），这将对组织有毒。我们研究了β-胡萝卜素、叶黄素和玉米黄质的CDA对人视网膜色素上皮细胞（ARPE-19）的细胞毒性作用。用CDA处理血清饥饿的ARPE-19细胞，检测细胞活力、细胞凋亡、活性氧（ROS）水平、核染色质凝聚和碎裂、线粒体膜电位（MMP）变化以及转录因子NF-κ B和AP-1的活化。我们观察到ARPE-19细胞与CDA孵育后细胞活力呈剂量和时间依赖性下降。CDA处理还以剂量依赖性方式导致ROS水平升高。CDA处理后，观察到大量凋亡细胞。CDA诱导的ARPE-19细胞早期凋亡变化与MMP的变化有关。在用CDA处理的细胞中也观察到核染色质浓缩和断裂增加。CDA对ARPE-19细胞的毒性可被抗氧化剂NAC显著减轻。此外，CDA诱导NF-κ B和AP-1的活化，而NAC显著抑制该活化。因此，我们的研究结果表明，CDA可以增加ARPE-19细胞中的氧化应激，通过升高ROS水平，这将导致细胞氧化还原状态的失衡，这可能导致细胞死亡。这表明，高类胡萝卜素补充治疗AMD应谨慎使用。(C)2007爱思唯尔有限公司保留所有权利。
Carotenoids have been advocated as potential therapeutic agents in treating age-related macular degeneration (AMD). In ocular tissues carotenoids may undergo oxidation and form carotenoid-derived aldehydes (CDA), which would be toxic to tissues. We have investigated the cytotoxic effects of CDA from P-carotene, Lutein and Zeaxanthin on human retinal pigment epithelial cells (ARPE-19). The serum-starved ARPE-19 cells were treated with CDA without or with antioxidant, N-acetylcysteine (NAC) and cell viability, apoptosis, reactive oxygen species (ROS) levels, nuclear chromatin condensation as well as fragmentation, change in mitochondrial membrane potential (MMP) and activation of transcription factors NF-kappa B and AP-1 were determined. We observed a dose and time-dependent decline in cell viability upon incubation of ARPE-19 cells with CDA. The CDA treatment also led to elevation in ROS levels in a dose-dependent manner. Upon CDA treatment a significant number of apoptotic cells were observed. Also early apoptotic changes in ARPE-19 cells induced by CDA were associated with change in MMP. Increased nuclear chromatin condensation and fragmentation were also observed in cells treated with CDA. The cytotoxicity of CDA in ARPE-19 cells was significantly ameliorated by the antioxidant, NAC. Furthermore, CDA induced the activation of NF-kappa B and AP-1 which was significantly inhibited by NAC. Thus our results demonstrate that CDA could increase the oxidative stress in ARPE-19 cells by elevating ROS levels that would cause imbalance in cellular redox status, which could lead to cell death. This would suggest that high carotenoid supplementation for treatment of AMD should be used cautiously. (C) 2007 Elsevier Ltd. All rights reserved.