Role of NF-E2-related factor 2 in retinal cell protection

doi:10.16098/j.issn.0529-1356.2017.05.021

Abstract

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

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.

References

［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.

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