NF-E2相关因子2对视网膜细胞保护作用的研究进展

doi:10.16098/j.issn.0529-1356.2017.05.021

摘要/Abstract

摘要：

核转录因子NF-E2相关因子2(Nrf2)介导的抗氧化还原通路在细胞氧化应激损伤过程中起到重要的保护作用。在氧化应激的刺激下，Nrf2可以启动多种细胞保护性基因的表达从而维持细胞稳态。因此，在治疗氧化应激损伤的疾病时，药物诱导Nrf2通路表达上调成为了一个新的研究方向。我们主要从视网膜神经细胞和视网膜血管内皮细胞两个方面总结了Nrf2在视网膜病变中的细胞保护作用的相关研究进展。

Abstract:

NF-E2-related factor 2 (Nrf2) is a redox sensitive transcription factor mediating many protective genes. The Nrf2-regulated antioxidant pathway has been found to be adaptively activated to counteract increased oxidative stress. Pharmacological induction of Nrf2 pathway has been implicated as a new therapeutic strategy to relieve cell damage. This review summarized the main findings on the protective role of Nrf2 in retinal diseases.

Key words: NF-E2-related factors 2, Retina, Oxidative stress, Retinal neuron, Retinal microvascular cell

庞仪琳张卫光张艳何美华. NF-E2相关因子2对视网膜细胞保护作用的研究进展[J]. 解剖学报, 2017, 48(5): 617-621.

PANG Yi-lin ZHANG Wei-guang ZHANG Yan HE Mei-hua. Role of NF-E2-related factor 2 in retinal cell protection[J]. Acta Anatomica Sinica, 2017, 48(5): 617-621.

参考文献

［1］Moi P, Chan K, Asunis I, et al. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/API repeat of the beta-globin locus control region ［J］. Proc Natl Acad Sci USA, 1994, 91(21): 9926-9930.

［2］Jain AK, Bloom DA, Jaiswal AK. Nuclear import and export signals in control of Nrf2 ［J］. J Biol Chem, 2005, 280(32): 29158-29168.

［3］Cho HY, Reddy SP, Debiase A, et al. Gene expression profiling of Nrf2-mediated protection against oxidative injury ［J］. Free Radic Biol Med, 2005, 38(3): 325-343.

［4］Zhao Z, Chen Y, Wang J, et al. Age-related retinopathy in NRF2-deficient mice ［J］. PLoS One, 2011, 6(4): e19456.

［5］Wang L, Kondo N, Cano M, et al. Nrf2 signaling modulates cigarette smoke-induced complement activation in retinal pigmented epithelial cells［J］. Free Radic Biol Med, 2014, 5(70): 155-166.

［6］Aoyama K, Watabe M, Nakai T. Regulation of neuronal glutathione synthesis ［J］. Pharmacol Sci, 2008, 108(3): 227-238.

［7］Gao X, Talalay P. Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photo-oxidative damage ［J］, PNAS, 2004, 101(28): 10446-10450.［8］Sachdeva MM, Cano M, Handa JT. Nrf2 signaling is impaired in the aging RPE given an oxidative insult ［J］. Exp Eye Res, 2014, 2(119): 111-114.

［9］Zhong Q, Mishra M, Kowluru RA. Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy ［J］. Invest Ophthalmol Vis Sci, 2013, 54(6): 3941-3943.

［10］Zou X, Feng Z, Li Y, et al. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways ［J］. Nutr Biochem, 2012, 23(8): 994-1006.

［11］Hanus J, Kolkin A, Chimienti J, et al. 4-acetoxyphenol prevents RPE oxidative stress-induced necrosis by functioning as an NRF2 stabilizer ［J］. Invest Ophthalmol Vis Sci, 2015, 56(9): 5048-5059.

［12］Zhu C, Wang S, Wang B, et al.17β-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling pathways to suppress light-induced degeneration in rat retina ［J］. Neuroscience, 2015, 9(304): 328-339.

［13］ou X, Gao J, Zheng Y, et al. Zeaxanthin induces Nrf2-mediated phase Ⅱ enzymes in protection of cell death ［J］. Cell Death Dis, 2014, 8(5): e1218

［14］Li Z, Dong X, Liu H, et al. Astaxanthin protects ARPE-19 cells from oxidative stress via upregulation of Nrf2-regulated phase II enzymes through activation of PI3K/Akt ［J］. Mol Vis, 2013, 25(19): 1656-1666.

［15］Tanito M, Agbaga MP, Anderson RE. Up-regulation of thioredoxin system via Nrf2-antioxidant responsive element pathway in adaptive-retinal neuroprotection in vivo and in vitro ［J］. Free Radic Biol Med, 2007, 42(12): 1838-1850.

［16］Tanito M, Masutani H, Kim YC, e tal. Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice ［J］. Invest Ophthalmol Vis Sci, 2005, 46(3): 979-987.

［17］Kong L, Tanito M, Huang Z, et al. Delay of photoreceptor degeneration in tubby mouse by sulforaphane ［J］. Neurochem, 2007, 101(4): 1041-1052.

［18］Mandal MN, Patlolla JM, Zheng L, et al. Curcumin protects retinal cells from light-and oxidant stress-induced cell death ［J］. Free Radic Biol Med, 2009, 46(5): 672-679.

［19］Rezaie T, McKercher SR, Kosaka K. Protective effect of carnosic acid, a pro-electrophilic compound, in models of oxidative stress and light-induced retinal degeneration ［J］. Invest Ophthalmol Vis Sci, 2012, 53(12):7847-7854.

［20］Xiong W, MacColl Garfinkel AE, Li Y, et al. NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage ［J］. Clin Invest, 2015, 125(4): 1433-1445.

［21］He M, Pan H, Chang RC，et al. Activation of the Nrf2/HO-1 antiox idant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage ［J］. PLoS One, 2014, 9(1): e84800.

［22］Pan H, He M, Liu R, et al. Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway ［J］. PLoS One, 2014, 9(12): e114186.

［23］Liu Y, Tang L, Chen B. Effects of antioxidant gene therapy on retinal neurons and oxidative stress in a model of retinal ischemia/reperfusion ［J］. Free Radic Biol Med, 2012, 52(5): 909-915.

［24］Himori N, Yamamoto K, Maruyama K, et al. Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death ［J］. Neurochem, 2013, 127(5): 669-680.

［25］Xu Z, Wei Y, Gong J, et al. NRF2 plays a protective role in diabetic retinopathy in mice ［J］. Diabetologia, 2014, 57(1): 204-213.

［26］Xu Z, Cho H, Hartsock MJ, et al. Neuroprotective role of Nrf2 for retinal ganglion cells in ischemia-reperfusion ［J］. Neurochem, 2015, 133(2): 233-241.

［27］Huang C, Zhang P, Wang W, et al. Long-term blue light exposure induces RGC-5 cell death in vitro: involvement of mitochondria-dependent apoptosis, oxidative stress, and MAPK signaling pathways ［J］. Apoptosis, 2014, 19(6): 922-932.

［28］Cao Y, Li X, Wang CJ, et al. Role of NF-E2-related factor 2 in neuroprotective effect of l-carnitine against high glucose-induced oxidative stress in the retinal ganglion cells ［J］. Biomed Pharmacother, 2015, 69: 345-348.

［29] Xu Z, Wei Y, Gong J,et al. NRF2 plays a protective role in diabetic retinopathy in mice ［J］. Diabetologia, 2014, 57(1): 204-213

［30］Tan SM, Deliyanti D, Figgett WA, et al. Ebselen by modulating oxidative stress improves hypoxia-induced macroglial Muller cell and vascular injury in the retina ［J］. Exp Eye Res, 2015, 136: 1-8.

［31］Wang XL, Wang HD. Neuroprotection of Nrf2 in central nervous system disease ［J］. Journal of Medical Postgraduates, 2011, 24(7): 754-757. (in Chinese)

王笑亮,王汉东. Nrf2在中枢神经系统疾病中的神经保护作用［J］. 医学研究生学报, 2011,24(7): 754-757.

［32］Arai-Gaun S, Katai N, Kikuchi T, et al. Heme oxygenase-1 induced in muller cells plays a protective role in retinal ischemia-reperfusion injury in rats ［J］. Invest Ophthalmol Vis Sci, 2004, 45(11): 4226-4232.

［33］Chen K, Gunter K, Maines MD. Neurons overexpressing hemeoxygenase-1 resist oxidative stress-mediated cell death ［J］. J Neurochem, 2000, 75(1): 304-313.

［34］Sun MH, Pang TH, Chen SL, et al. Retinal protection from acute glaucoma-induced Ischemia-reperfusion injury through pharmacologic induction of heme oxygenase-1 ［J］. Invest Ophthalmol Vis Sci, 2010, 51(9): 4798-4808.

［35］Zeng Z, Huang HF, Chen MQ, et al. Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury: the role of Kupffer cells ［J］. World J Gastroenterol, 2010, 16(10): 1285-1292.

［36］Wei Y, Gong J, Yoshida T. Nrf2 has a protective role against neuronal and capillary degeneration in retinal ischemia-reperfusion injury ［J］. Free Radic Biol Med, 2011, 51(1): 216-224.

［37］Uno K, Prow TW, Bhutto IA, et al. Role of Nrf2 in retinal vascular development and the vaso-obliterative phase of oxygen-induced retinopathy ［J］. Exp Eye Res, 2010, 90(4): 493-500.

［38］Wei Y, Gong J, Thimmulappa RK, et al. Nrf2 acts cell-autonomously in endothelium to regulate tip cell formation and vascular branching ［J］. Proc Natl Acad Sci USA, 2013, 110(41): e3910-3918.

［39］Wei Y, Gong J, Xu Z, et al. Nrf2 in ischemic neurons promotes retinal vascular regeneration through regulation of semaphorin 6A ［J］. Proc Natl Acad Sci USA, 2015, 112(50): 6927-6936.

[1]	冯丽萍徐伊琳陈珣刘大海王军勇王晓瑛林金杏. 斑马鱼视网膜微细结构及发育特征[J]. 解剖学报, 2024, 55(1): 105-112.
[2]	张琴杨俊霞蒋青松. 福辛普利对糖尿病视网膜病变小鼠血管紧张素转化酶2和血管内皮生长因子的影响[J]. 解剖学报, 2023, 54(6): 628-634.
[3]	庄海容吴子东陈雪红李成军. 舒洛地特对大鼠糖尿病视网膜病变的修复及MAPK通路的调节作用[J]. 解剖学报, 2023, 54(4): 392-399.
[4]	张小丽张书强徐绘 . 视网膜Müller细胞重编程研究进展[J]. 解剖学报, 2023, 54(4): 484-489.
[5]	李薇王丽汪志华刘庆春韩荣胜 . 长链非编码RNA alpha-2-巨球蛋白反义RNA 1靶向微小RNA-106b-5p调控氧化型低密度脂蛋白诱导的人脑微血管内皮细胞损伤[J]. 解剖学报, 2023, 54(3): 319-327.
[6]	谢秋敏孙艳婷许皓刘蕙文易勤谭彬田杰朱静. 低氧低糖及血清剥夺联合处理抑制Nrf2信号通路诱发大鼠骨髓间充质干细胞氧化应激和凋亡[J]. 解剖学报, 2023, 54(3): 305-312.
[7]	郭东铭张静文黄新磊徐杨熊天庆曹文宇梁景岩 . 瞬时感受器电位香草素受体亚家族Ⅳ型抑制剂HC067047对脂多糖诱导的小鼠焦虑样行为的影响[J]. 解剖学报, 2023, 54(2): 149-155.
[8]	雷蕾陆铉杨劲松尤玉珍梅燕. 组蛋白去乙酰化酶3抑制剂通过减轻氧化应激降低缺氧/复氧引起的PC12细胞凋亡[J]. 解剖学报, 2021, 52(5): 706-711.
[9]	李重阳苟陶然俞诗源. 枸杞水提液对海洛因损伤小鼠视网膜组织结构、诱导型一氧化氮合酶活性、Caspase-3及核因子κB蛋白表达的影响[J]. 解剖学报, 2021, 52(4): 554-560.
[10]	杨小荣高瑞君李艳丽殷丽天张策. 缺失第8外显子的SIRT1剪接体和SIRT1全长在293T细胞氧化损伤中的不同作用[J]. 解剖学报, 2020, 51(6): 855-860.
[11]	刘杰任瑜陈月刘菁向勤杨琴. 白藜芦醇对氧糖剥夺/再复氧损伤后体外小胶质细胞极化的影响[J]. 解剖学报, 2020, 51(3): 320-325.
[12]	邢鹏张娜赵静云张轶吕翠婷许碧莎. 白藜芦醇拮抗卵泡颗粒细胞氧化应激的损伤[J]. 解剖学报, 2020, 51(2): 189-194.
[13]	黄艳姣郑兰荣周永康. 脑源性神经营养因子和一氧化氮合酶在扬子鳄眼球中的定位和表达分析[J]. 解剖学报, 2019, 50(5): 561-564.
[14]	邱竹姜蓉汪子铃陈粼波陈雄斌王璐黄国宁王亚平. 当归多糖对D-半乳糖致衰老小鼠睾丸的保护作用[J]. 解剖学报, 2019, 50(4): 506-511.
[15]	伍洋刘英刘济滔尹德锋. 对氧磷酶3基因过表达对急性中毒小鼠肝损伤的保护作用及机制[J]. 解剖学报, 2019, 50(2): 179-184.