山东大学耳鼻喉眼学报 ›› 2021, Vol. 35 ›› Issue (3): 125-130.doi: 10.6040/j.issn.1673-3770.0.2020.191

• 临床研究 • 上一篇    

谷氧还蛋白在眼病中的作用研究进展

付奕豪1,2,徐逸轩1,2综述严宏1,3,张婕1审校   

  1. 1. 空军军医大学唐都医院 眼科, 陕西 西安 710038;
    2. 空军军医大学基础医学院, 陕西 西安 710032;
    3. 陕西省眼科医院/西北工业大学附属西安市第四医院, 陕西 西安 710004
  • 发布日期:2021-05-14
  • 通讯作者: 张婕. E-mail:jessicazhangjie@hotmail.com
  • 基金资助:
    国家自然科学基金青年科学项目(81300743)

Recent research advances in the role of glutaredoxin in oculopathy

FU Yihao1,2, XU Yixuan1,2Overview,YAN Hong1,3, ZHANG Jie1Guidance   

  1. 1. Department of Ophthalmonogy, Tangdu Hospital, Air Force Medical University, Xi'an 710038, Shaanxi, China;
    2. Basic Medical School, Air Force Medical University, Xi'an 710032, Shaanxi, China;
    3. Shaanxi Eye Hospital of Xi'an Fourth Hospital, Northwestern Polytechnical University, Xi'an 710004, Shaanxi, China
  • Published:2021-05-14

摘要: 谷氧还蛋白(Grx)是巯基-二硫化物氧化还原酶家族的重要一员,其主要功能是还原蛋白质和谷胱甘肽形成的二硫化物,从而维持细胞的氧化还原平衡。Grx存在于全身许多组织中。近年来,Grx在眼部疾病中发挥的保护功能和与其他抗氧化酶的协同作用不断被阐明,对于Grx有了更加深入的认识。综述主要总结了Grx在治疗眼病研究中所取得的最新进展。

关键词: 谷氧还蛋白, 氧化应激, 抗氧化酶, 白内障, 眼病, 基因敲除小鼠

Abstract: Glutaredoxin(Grx)is animportant member of the thiol disulfide oxidoreductase protein family. The primary function is to dethiolate glutathionylated proteins, thus maintaining cellular redox homeostasis. Grx is expressed in many tissues throughout the body. In recent years, the protective function of Grx in oculopathy and its synergistic effect with other antioxidative enzymes have been increasingly elucidated, leading to a better understanding of this protein. This review summarizes the latest research on the role of Grx in oculopathy.

Key words: Glutaredoxin, Oxidative stress, Antioxidase, Cataract, Oculopathy, Gene knockout mice

中图分类号: 

  • R77
[1] Williams LB, Prakalapakorn SG, Ansari Z et al. Impact and Trends in Global Ophthalmology[J]. Current Ophthalmology Reports, 2020, 22:1-8. doi: 10.1007/s40135-020-00245-x.
[2] Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration(AMD): associations with cardiovascular disease phenotypes and lipid factors[J]. Eye and Vision, 2016,3:34-53. doi: 10.1186/s40662-016-0063-5.
[3] Yang X, Pan X, Zhao X, et al.Autophagy and Age-Related Eye Diseases[J]. BioMed Research International, 2019, 2019(7601):1-12. doi:10.1155/2019/5763658.
[4] Askelöf P, Axelsson K, Eriksson S, et al. Mechanism of action of enzymes catalyzing thiol-disulfide interchange. Thioltransferases rather than transhydrogenases[J]. FEBS Lett, 1974, 38(3): 263-267. doi:10.1016/0014-5793(74)80068-2.
[5] Holmgren A. Hydrogen donor system for Escherichia coli ribonucleoside-diphosphate reductase dependent upon glutathione[J]. Proc Natl Acad Sci USA, 1976, 73(7): 2275-2279. doi:10.1073/pnas.73.7.2275.
[6] Holmgren A. Thioredoxin[J]. Annu Rev Biochem, 1985, 54: 237-271. doi:10.1146/annurev.bi.54.070185.001321.
[7] Lou MF. Protein-thiol mixed disulfides and thioltransferase in the Lens[M] //Advances in Ocular Toxicology. Boston, MA: Springer US, 1997: 27-46. doi:10.1007/978-1-4615-5937-5_4.
[8] Gladyshev VN, Liu A, Novoselov SV, et al. Identification and characterization of a new mammalian glutaredoxin(thioltransferase), Grx2[J]. J Biol Chem, 2001, 276(32): 30374-30380. doi:10.1074/jbc.M100020200.
[9] Lundberg M, Johansson C, Chandra J, et al. Cloning and expression of a novel human glutaredoxin(Grx2)with mitochondrial and nuclear isoforms[J]. J Biol Chem, 2001, 276(28): 26269-26275. doi:10.1074/jbc.M011605200.
[10] Holmgren A. Glutathione-dependent synthesis of deoxyribonucleotides. Characterization of the enzymatic mechanism of Escherichia coli glutaredoxin[J]. J Biol Chem, 1979, 254(9): 3672-3678. doi:10.1016/0031-9422(80)87056-7.
[11] Holmgren A. Glutathione-dependent synthesis of deoxyribonucleotides. Purification and characterization of glutaredoxin from Escherichia coli[J] J Biol Chem, 1979, 254(9): 3664-3671. doi:10.1016/0031-9422(80)87056-7.
[12] Yoshitake S, Nanri H, Fernando MR, et al. Possible differences in the regenerative roles played by thioltransferase and thioredoxin for oxidatively damaged proteins[J]. J Biochem, 1994, 116(1): 42-46. doi: 10.1093/oxfordjournals.jbchem.a124500.
[13] Wu F, Wang GM, Raghavachari N, et al. Distribution of thioltransferase(glutaredoxin)in ocular tissues[J]. Invest Ophthalmol Vis Sci, 1998, 39(3): 476-480. doi: 10.1097/00004397-199838020-00016.
[14] Xing KY, Lou MF. Effect of age on the thioltransferase(glutaredoxin)and thioredoxin systems in the human Lens[J]. Invest Ophthalmol Vis Sci, 2010, 51(12): 6598-6604. doi:10.1167/iovs.10-5672.
[15] Lei XG, Zhu JH, Cheng WH, et al. Paradoxical roles of antioxidant enzymes: basic mechanisms and health implications[J]. Physiol Rev, 2016, 96(1): 307-364. doi:10.1152/physrev.00010.2014.
[16] Scalcon V, Tonolo F, Folda A, et al. Dimers of glutaredoxin 2 as mitochondrial redox sensors in selenite-induced oxidative stress[J]. Metallomics, 2019, 11(7): 1241-1251. doi:10.1039/c9mt00090a.
[17] 夏海燕,黄子维,李宽钰.谷氧还蛋白2与人类健康[J].生命科学,2014,26(1):72-79. doi:10.13376/j.cbls/2014011. XIA Haiyan, HUANG Ziwei, LI Kuanyu. Role of glutaredoxin2 in human health and diseases[J]. Chinese Bulletin of Life Sciences, 2014, 26(1): 72-79. doi: 10.13376/j.cbls/2014011.
[18] Reddy VN. Glutathione and its function in the lens- an overview[J]. Exp Eye Res 1990, 50(6): 771-778. doi:10.1016/0014-4835(90)90127-G.
[19] Giblin FJ. Glutathione: a vital Lens antioxidant[J]. J Ocul Pharmacol Ther, 2000, 16(2): 121-135. doi:10.1089/jop.2000.16.121.
[20] Lou MF. Thiol regulation in the Lens[J]. J Ocul Pharmacol Ther, 2000, 16(2): 137-148. doi:10.1089/jop.2000.16.137.
[21] 张婕, 严宏, Lou MF. 硫醇转移酶基因敲除小鼠模型的建立及其白内障形成机制[J]. 国际眼科杂志. 2020, 20(3):420-425. doi: 10.3980/j.issn.1672-5123.2020.3.05. ZHANG Jie, YAN Hong, Lou MF. Establishment of Thioltransferase knockout mouse model and the function of thioltransferase in cataratogenesis[J]. Int Eye Sci, 2020, 20(3):420-425. doi: 10.3980/j.issn.1672-5123.2020.3.05.
[22] Kronschläger M, Galichanin K, Ekström J, et al. Protective effect of the thioltransferase gene on in vivo UVR-300 nm-induced cataract[J]. Invest Ophthalmol Vis Sci, 2012, 53(1): 248-252. doi:10.1167/iovs.11-8504.
[23] Zhang J, Yan H, Löfgren S, et al. Ultraviolet radiation-induced cataract in mice: the effect of age and the potential biochemical mechanism[J]. Invest Ophthalmol Vis Sci, 2012, 53(11): 7276-7285. doi:10.1167/iovs.12-10482.
[24] Moon S, Fernando MR, Lou MF. Induction of thioltransferase and thioredoxin/thioredoxin reductase systems in cultured porcine lenses under oxidative stress[J]. Invest Ophthalmol Vis Sci, 2005, 46(10): 3783-3789. doi:10.1167/iovs.05-0237.
[25] Wei M, Xing KY, Fan YC, et al. Loss of thiol repair systems in human cataractous lenses[J]. Invest Ophthalmol Vis Sci, 2014, 56(1): 598-605. doi:10.1167/iovs.14-15452.
[26] 廖萱, 赵敏. 巯基转移酶在年龄相关性白内障晶状体上皮细胞中的表达研究[J]. 华西医学, 2009, 24(6): 1359-1362. LIAO Xuan, ZHAO Min. Expression of thioltransferase in Lens epithelial cells of age-related cataract[J]. West China Medical Journal, 2009, 24(6): 1359-1362.
[27] Fan Q, Zhang YL, Liu YF, et al. Glutaredoxin desensitizes Lens to oxidative stress by connecting and integrating specific signaling and transcriptional regulation for antioxidant response[J]. Cell Physiol Biochem, 2016, 39(5): 1813-1826. doi:10.1159/000447881.
[28] 李凤杰, 沈丽君, 方合志, 等. 线粒体呼吸链复合体1[J]. 中国细胞生物学报,2014, 36(8):1153-1161. doi: 10.11844/cjcb.2014.08.0037. LI Fengjie, SHEN Lijun, FANG Hezhi, et al. Mitochondrial Respiratory Complex I[J]. Chinese Journal of Cell Biology, 2014, 36(8):1153-1161. doi:10.11844/cjcb.2014.08.0037.
[29] Wu HL, Xing KY, Lou MF. Glutaredoxin 2 prevents H2O2-induced cell apoptosis by protecting complex I activity in the mitochondria[J]. Biochim Biophys Acta, 2010, 1797(10):1705-1715. doi: 10.1016/j.bbabio.2010.06.003.
[30] Wu HL, Yu YB, David L, et al. Glutaredoxin 2(Grx2)gene deletion induces early onset of age-dependent cataracts in mice[J]. J Biol Chem, 2014, 289(52): 36125-36139. doi:10.1074/jbc.M114.620047.
[31] Wu HL, Lin LR, Giblin F, et al. Glutaredoxin 2 knockout increases sensitivity to oxidative stress in mouse Lens epithelial cells[J]. Free Radic Biol Med, 2011, 51(11): 2108-2117. doi: 10.1016/j.freeradbiomed.2011.09.011.
[32] Tarr JM, Kaul K, Chopra M, et al. Pathophysiology of diabetic retinopathy[J]. ISRN Ophthalmol, 2013: 1-13. doi:10.1155/2013/343560.
[33] 于罡,严宏. 硫醇转移酶对高糖诱导大鼠晶状体氧化应激的保护作用[J]. 国际眼科杂志, 2014, 14(11): 1927-1930. doi:10.3980/j.issn.1672-5123.2014.11.03. YU Gang, YAN Hong. Protective effects of thiohransferase in rat lens incubated with high glucose[J]. Guoji Yanke Zazhi(Int Eye Sci), 2014, 14(11):1927-1930. doi:10.3980/j.issn.1672-5123.2014.11.03.
[34] Zhang J, Yan H, Lou MF. Does oxidative stress play any role in diabetic cataract formation? - Re-evaluation using a thioltransferase gene knockout mouse model[J]. Exp Eye Res, 2017, 161: 36-42. doi: 10.1016/j.exer.2017.05.014.
[35] Potilinski MC, Lorenc V, Perisset S, et al. Mechanisms behind retinal ganglion cell loss in diabetes and therapeutic approach[J]. Int J Mol Sci, 2020, 21(7): E2351. doi:10.3390/ijms21072351.
[36] Shelton MD, Kern TS, Mieyal JJ. Glutaredoxin regulates nuclear factor kappa-B and intercellular adhesion molecule in Müller cells: model of diabetic retinopathy[J]. J Biol Chem, 2007, 282(17): 12467-12474. doi:10.1074/jbc.M610863200.
[37] Shelton MD, Distler AM, Kern TS, et al. Glutaredoxin regulates autocrine and paracrine proinflammatory responses in retinal glial(muller)cells[J]. J Biol Chem, 2009, 284(8): 4760-4766. doi:10.1074/jbc.M805464200.
[38] Zhao WH, Xu WM. Glutaredoxin 2(GRX2)deficiency exacerbates high fat diet(HFD)-induced insulin resistance, inflammation and mitochondrial dysfunction in brain injury: a mechanism involving GSK-3β[J]. Biomedecine Pharmacother, 2019, 118: 108940. doi: 10.1016/j.biopha.2019.108940.
[39] Jager RD, Mieler WF, Miller JW. Age-related macular degeneration[J]. N Engl J Med, 2008, 358(24): 2606-2617. doi:10.1056/NEJMra0801537.
[40] Liu XB, Jann J, Xavier C, et al. Glutaredoxin 1(Grx1)protects human retinal pigment epithelial cells from oxidative damage by preventing AKT glutathionylation[J]. Invest Ophthalmol Vis Sci, 2015, 56(5): 2821-2832. doi:10.1167/iovs.14-15876.
[41] Liu XB, Xavier C, Jann J, et al. Salvianolic acid B(sal B)protects retinal pigment epithelial cells from oxidative stress-induced cell death by activating glutaredoxin 1(Grx1)[J]. Int J Mol Sci, 2016, 17(11): E1835. doi:10.3390/ijms17111835.
[42] 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, 304: 328-339. doi: 10.1016/j.neuroscience.2015.07.057.
[43] Nakagami Y. Nrf2 is an attractive therapeutic target for retinal diseases[J]. Oxid Med Cell Longev, 7469326. doi:10.1155/2016/7469326.
[44] Ouyang YF, Peng Y, Li J, et al. Modulation of thiol-dependent redox system by metal ions via thioredoxin and glutaredoxin systems[J]. Metallomics, 2018, 10(2): 218-228. doi:10.1039/c7mt00327g.
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