Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress
Melatonin protects human retinal pigment epithelial (RPE) cells against oxidative stress
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DOI：
10.1016/j.exer.2004.02.003
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发表时间：
2004-06-01
影响因子：
3.4
通讯作者：
Godley, BF
中科院分区：
文献类型：
--
作者：
Liang, FQ;Green, L;Godley, BF
氧化应激参与老年性黄斑变性（AMD）的发病机制。常规抗氧化剂的管理已被证明可以减缓AMD和视力丧失的进展。褪黑素是一种由松果体和视网膜产生的内源性神经激素，据报道是一种有效的抗氧化剂和自由基清除剂。在这项研究中，我们测试了褪黑激素是否可以保护视网膜色素上皮细胞免受过氧化氢（H2O2）诱导的细胞死亡。由于线粒体DNA （mtDNA）优先受到氧化损伤，我们测试了褪黑激素是否可以减少h2o2诱导的mtDNA损伤。培养人RPE细胞系（ARPE-19），分别暴露于H2O2（100和200 muM）中1小时，诱导细胞死亡。在H2O2处理之前，细胞用不同浓度（0.1 - 200 muM）的褪黑激素处理2、24或72小时。对照细胞分别接受褪黑素或乙醇。MTT法测定细胞活力，结果显示，接受两种浓度的褪黑激素预处理2小时和24小时的细胞对H2O2毒性没有显著（P > 0.05）的保护作用。然而，当连续3天每天给予褪黑素时，这种延长的治疗明显减少h2o2诱导的细胞死亡（P < 0.05）。通过定量PCR评估，与未接受褪黑激素治疗的RPE细胞相比，经褪黑激素预处理的RPE细胞MtDNA损伤显著降低（P = 0.031）。这些结果表明，褪黑激素可能在保护RPE细胞免受氧化应激方面发挥作用。(C) 2004 Elsevier Ltd.版权所有。
Oxidative stress is involved in the pathogenesis of age-related macular degeneration (AMD). Administration of conventional antioxidants has been shown to slow the progression of AMD and vision loss. Melatonin, an endogenous neurohormone produced by the pineal gland and retina, has been reported to be a potent antioxidant and free radical scavenger. In this study we tested whether melatonin can protect retinal pigment epithelial (RPE) cells against hydrogen peroxide (H2O2)-induced cell death. Since mitochondrial DNA (mtDNA) is preferentially susceptible to oxidative damage, we tested whether melatonin can reduce H2O2-induced mtDNA lesions. A human RPE cell line (ARPE-19) was cultured and exposed to H2O2 (100 and 200 muM) for 1 hr to induce cell death. Prior to H2O2 treatment, cells were treated with various concentrations (0.1 - 200 muM) of melatonin for 2, 24 or 72 hr. Control cells received either melatonin or ethanol alone. Cell viability, as determined by MTT assay, showed no significant (P > 0.05) protection against H2O2 toxicity in cells receiving 2- and 24-hr pretreatment of melatonin at either concentration. However, when melatonin was administered diurnally for 3 consecutive days, this prolonged treatment markedly reduced H2O2-induced cell death (P < 0.05). MtDNA damage, as assessed with quantitative PCR, was significantly decreased (P = 0.031) in RPE cells pretreated with melatonin as compared to those without melatonin treatment. These results suggest that melatonin may play a role in protecting RPE cells from oxidative stress. (C) 2004 Elsevier Ltd. All rights reserved.