胞外超氧化物歧化酶(EC-SOD)抗辐射作用的研究进展

摘要/Abstract

摘要： 电磁辐射、电离辐射、光辐射等辐射导致的组织器官损伤过程中常伴有活性氧(ROS)的激活和DNA损伤,而超氧化物歧化酶(SOD)是生物体内广泛存在的一种抗氧化金属酶,在氧化-抗氧化平衡调控中发挥着重要的作用,并且参与了众多疾病的发生与发展,其中胞外超氧化物歧化酶(EC-SOD)主要分布于细胞外基质中。大量研究表明EC-SOD在多种组织器官的辐射损伤中发挥着抗辐射的作用,其主要通过降低ROS水平、抗血管生成,抗趋化和抗炎等方式防止细胞和组织的进一步损伤。因此,本文将对EC-SOD及其模拟物或类似物在辐射防护中的保护作用及其机制进行综述,为EC-SOD应用于辐射防护提供理论参考。

关键词: 胞外超氧化物歧化酶, 辐射损伤, 抗辐射, 活性氧

Abstract: The tissue and organ damage process caused by electromagnetic radiation, ionizing radiation, optical radiation, and other radiation is often accompanied by reactive oxygen species (ROS) activation and DNA damage. Superoxide dismutase (SOD) is an antioxidant metalloenzyme that exists in the organism, which plays a vital role in the body’s oxidant/antioxidant balance, and participates in the occurrence and development of many diseases. Extra-cellular superoxide dismutase (EC-SOD) is mainly found in the extra-cellular matrix. Many studies have demonstrated that EC-SOD plays a protective role in radiation damage to a variety of tissues and organs, which mainly prevents further damage to cells and tissues by reducing ROS levels, anti-angiogenesis, anti-chemotactic and anti-inflammatory. Therefore, we have reviewed the protective role and mechanism of EC-SOD and its mimetics or analogues in radiation protection, and provide a theoretical reference for the application of EC-SOD with radiation resistance.

Key words: extra-cellular superoxide dismutase (EC-SOD), radiation injury, radiation resistance, reactive oxygen species(ROS)

中图分类号:

R142+.4

朱梦梅, 欧阳涛, 华天桢, 李琨, 于兵. 胞外超氧化物歧化酶(EC-SOD)抗辐射作用的研究进展[J]. 辐射防护, 2022, 42(2): 102-110.

ZHU Mengmei, OUYANG Tao, HUA Tianzhen, LI Kun, YU Bing. Research progress of EC-SOD radiation resistance[J]. RADIATION PROTECTION, 2022, 42(2): 102-110.

参考文献

[1] Singh V K, Newman V L, Romaine P L, et al. Use of biomarkers for assessing radiation injury and efficacy of countermeasures[J]. Expert Rev Mol Diagn. 2016, 16(1):65-81. DOI: 10.1586/14737159.2016.1121102.
[2] Anuranjani, Bala M. Concerted action of Nrf2-ARE pathway, MRN complex, HMGB1 and inflammatory cytokines - implication in modification of radiation damage[J]. Redox Biology, 2014, 2(8):32-46. DOI: 10.1016/j.redox.2014.02.008.
[3] Antonic V, Rabbani Z N, Jackson I L, et al. Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury[J]. Free Radic Res, 2015, 49(10):1259-1268. DOI: 10.3109/10715762.2015.1066501.
[4] Malaker K, Das R M. The effect of superoxide dismutase on the pathogenesis of radiation-induced pulmonary damage in the rat[J]. Pharmacol Ther, 1988, 39(1-3):327-330. DOI: 10.1016/0163-7258(88)90079-4.
[5] Borgstahl G E O, Oberley-Deegan R E. Superoxide dismutases (SODs) and SOD mimetics[J]. Antioxidants (Basel), 2018, 7(11):156-172. DOI: 10.3390/antiox7110156.
[6] Parascandolo A, Rappa F, Cappello F, et al. Extracellular superoxide dismutase expression in papillary thyroid cancer mesenchymal stem/stromal cells modulates cancer cell growth and migration[J]. Sci Rep, 2017, 7(4):14-16. DOI: 10.1038/srep41416.
[7] Fisher C L, Hallewell R A, Roberts V A, et al. Probing the structural basis for enzyme-substrate recognition in Cu,Zn superoxide dismutase[J]. Free Radic Res Commun, 1991, 12(1):287-296. DOI: 10.3109/10715769109145797.
[8] Ribera-Fonseca A, Inostroza-Blancheteau C, Cartes P, et al. Early induction of Fe-SOD gene expression is involved in tolerance to Mn toxicity in perennial ryegrass[J]. Plant Physiol Biochem, 2013, 7(3):77-82. DOI: 10.1016/j.plaphy.2013.08.012.
[9] Azadmanesh J, Borgstahl G E O. A review of the catalytic mechanism of human manganese superoxide dismutase[J]. Antioxidants (Basel), 2018, 7(2):25-36. DOI: 10.3390/antiox7020025.
[10] Miao L, St Clair D K. Regulation of superoxide dismutase genes: implications in disease[J]. Free Radic Biol Med, 2009, 47(4):344-356. DOI: 10.1016/j.freeradbiomed.2009.05.018.
[11] Marklund S L. Human copper-containing superoxide dismutase of high molecular weight[J]. Proc Natl Acad Sci U S A, 1982, 79:7634-7638. DOI: 10.1073/pnas.79.24.7634.
[12] Batinić-Haberle I, Rebouças J S, Spasojević I. Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential[J]. Antioxid Redox Signal, 2010, 13(6):877-918. DOI: 10.1089/ars.2009.2876.
[13] Bonetta R. Potential therapeutic applications of MnSODs and SOD-mimetics[J]. Chemistry, 2018, 24(20):5032-5041. DOI: 10.1002/chem.201704561.
[14] Allawzi A, McDermott I, Delaney C, et al. Redistribution of EC-SOD resolves bleomycin-induced inflammation via increased apoptosis of recruited alveolar macrophages[J]. FASEB J, 2019, 33(12):13465-13475. DOI: 10.1096/fj.201901038RR.
[15] Paital B, Sablok G, Kumar S, et al. Investigating the conformational structure and potential site interactions of SOD inhibitors on Ec-SOD in marine mud crab scylla serrata: A molecular modeling approach[J]. Interdiscip Sci, 2016, 8(3):312-318. DOI: 10.1007/s12539-015-0110-2.
[16] Levin E D. Extracellular superoxide dismutase (EC-SOD) quenches free radicals and attenuates age-related cognitive decline: opportunities for novel drug development in aging[J]. Curr Alzheimer Res, 2005, 2(2):191-196. DOI: 10.2174/1567205053585710.
[17] Cheng Y K, Hwang G Y, Lin C D, et al. Altered expression profile of superoxide dismutase isoforms in nasal polyps from nonallergic patients[J]. Laryngoscope, 2006, 116(3):417-422. DOI: 10.1097/01.MLG.0000199738.37455.55.
[18] Rola R, Zou Y, Huang T T, et al. Lack of extracellular superoxide dismutase (EC-SOD) in the microenvironment impacts radiation-induced changes in neurogenesis[J]. Free Radic Biol Med, 2007, 42(8):1133-1145. DOI: 10.1016/j.freeradbiomed.2007.01.020.
[19] Zou Y, Corniola R, Leu D, et al. Extracellular superoxide dismutase is important for hippocampal neurogenesis and preservation of cognitive functions after irradiation[J]. Proc Natl Acad Sci USA, 2012, 109(52):21522-21527. DOI: 10.1073/pnas.1216913110.
[20] Kang S K, Rabbani Z N, Folz R J, et al. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury[J]. Int J Radiat Oncol Biol Phys, 2003, 57(4):1056-1066. DOI: 10.1016/s0360-3016(03)01369-5.
[21] Lazarov O, Hollands C. Hippocampal neurogenesis: Learning to remember[J]. Prog Neurobiol, 2016, 138(140):1-18. DOI: 10.1016/j.pneurobio.2015.12.006.
[22] Zou Y, Leu D, Chui J, et al. Effects of altered levels of extracellular superoxide dismutase and irradiation on hippocampal neurogenesis in female mice[J]. Int J Radiat Oncol Biol Phys, 2013, 87(4):777-784. DOI: 10.1016/j.ijrobp.2013.08.002.
[23] Lierova A, Jelicova M, Nemcova M, et al. Cytokines and radiation-induced pulmonary injuries[J]. J Radiat Res, 2018, 59(6):709-753. DOI: 10.1093/jrr/rry067.
[24] Trott K R, Herrmann T, Kasper M. Target cells in radiation pneumopathy[J]. Int J Radiat Oncol Biol Phys, 2004, 58(2):463-469. DOI: 10.1016/j.ijrobp.2003.09.045.
[25] Beach T A, Groves A M, Johnston C J, et al. Recurrent DNA damage is associated with persistent injury in progressive radiation-induced pulmonary fibrosis[J]. Int J Radiat Biol, 2018, 94(12):1104-1115. DOI: 10.1080/09553002.2018.1516907.
[26] Shrishrimal S, Kosmacek E A, Oberley-Deegan R E. Reactive oxygen species drive epigenetic changes in radiation-induced fibrosis[J]. Oxid Med Cell Longev, 2019, 2019:1-27.DOI: 10.1155/2019/4278658.
[27] Rabbani Z N, Anscher M S, Folz R J, et al. Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity[J]. BMC Cancer, 2005, 5(1):59-67. DOI: 10.1186/1471-2407-5-59.
[28] Lange C, Brunswig-Spickenheier B, Cappallo-Obermann H, et al. Radiation rescue: mesenchymal stromal cells protect from lethal irradiation[J]. Plos One, 2011, 6(1):14-86. DOI: 10.1371/journal.pone.0014486.
[29] Chinnadurai R, Forsberg M H, Kink J A, et al. Use of MSCs and MSC-educated macrophages to mitigate hematopoietic acute radiation syndrome[J]. Curr Stem Cell Rep, 2020, 6(3):77-85. DOI: 10.1007/s40778-020-00176-0.
[30] Sah S K, Agrahari G, Kim T Y. Insights into superoxide dismutase 3 in regulating biological and functional properties of mesenchymal stem cells[J]. Cell Biosci, 2020, 10(1):1-12. DOI: 10.1186/s13578-020-00386-3.
[31] Agrahari G, Sah S K, Kim T Y. Superoxide dismutase 3 protects mesenchymal stem cells through enhanced autophagy and regulation of FoxO3a trafficking[J]. BMB Rep, 2018, 51(7):344-349. DOI: 10.5483/bmbrep.2018.51.7.078.
[32] Gan J, Meng F, Zhou X, et al. Hematopoietic recovery of acute radiation syndrome by human superoxide dismutase-expressing umbilical cord mesenchymal stromal cells[J]. Cytotherapy, 2015, 17(4):403-417. DOI: 10.1016/j.jcyt.2014.11.011.
[33] Hu K X, Sun Q Y, Guo M, et al. The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury[J]. Br J Radiol, 2010, 83(985):52-58. DOI: 10.1259/bjr/61042310.
[34] Matsumura Y, Ananthaswamy H N. Toxic effects of ultraviolet radiation on the skin[J]. Toxicol Appl Pharmacol, 2004, 195(3):298-308. DOI: 10.1016/j.taap.2003.08.019.
[35] Mancebo S E, Wang S Q. Skin cancer: role of ultraviolet radiation in carcinogenesis[J]. Rev Environ Health, 2014, 29(3):265-273. DOI: 10.1515/reveh-2014-0041.
[36] Kim H Y, Sah S K, Choi S S, et al. Inhibitory effects of extracellular superoxide dismutase on ultraviolet B-induced melanogenesis in murine skin and melanocytes[J]. Life Sci, 2018, 210: 201-208. DOI: 10.1016/j.lfs.2018.08.056.
[37] Nguyen N H, Tran G B, Nguyen C T. Anti-oxidative effects of superoxide dismutase 3 on inflammatory diseases[J]. J Mol Med (Berl), 2020, 98(1):59-69. DOI: 10.1007/s00109-019-01845-2.
[38] Kim Y, Kim B H, Lee H, et al. Regulation of skin inflammation and angiogenesis by EC-SOD via HIF-1α and NF-κB pathways[J]. Free Radic Biol Med, 2011, 51(11):1985-1995. DOI: 10.1016/j.freeradbiomed.2011.08.027.
[39] Choung B Y, Byun S J, Suh J G, et al. Extracellular superoxide dismutase tissue distribution and the patterns of superoxide dismutase mRNA expression following ultraviolet irradiation on mouse skin[J]. Exp Dermatol, 2004, 13(11):691-699. DOI: 10.1111/j.0906-6705.2004.00209.x.
[40] Singh M, Alavi A, Wong R, et al. Radiodermatitis: A review of our current understanding[J]. Am J Clin Dermatol, 2016, 17(3):277-292. DOI: 10.1007/s40257-016-0186-4.
[41] Amber K T, Shiman M I, Badiavas E V. The use of antioxidants in radiotherapy-induced skin toxicity[J]. Integr Cancer Ther, 2014, 13(1):38-45. DOI: 10.1177/1534735413490235.
[42] Doctrow S R, Lopez A, Schock A M, et al. A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin[J]. J Invest Dermatol, 2013, 133(4):1088-1096. DOI: 10.1038/jid.2012.410.
[43] Manzanas García A, LÓpez Carrizosa M C, Vallejo Ocaũa C, et al. Superoxidase dismutase (SOD) topical use in oncologic patients: treatment of acute cutaneous toxicity secondary to radiotherapy[J]. Clin Transl Oncol, 2008, 10(3):163-167. DOI: 10.1007/s12094-008-0174-0.
[44] Baskar R, Lee K A, Yeo R, et al. Cancer and radiation therapy: current advances and future directions[J]. Int J Med Sci, 2012, 9(3):193-199. DOI: 10.7150/ijms.3635. Epub 2012 Feb 27.
[45] Gandhi S, Chandna S. Radiation-induced inflammatory cascade and its reverberating crosstalks as potential cause of post-radiotherapy second malignancies[J]. Cancer Metastasis Rev, 2017, 36(2):375-393. DOI: 10.1007/s10555-017-9669-x.
[46] Blyth B J, Cole A J, MacManus M P, et al. Radiation therapy-induced metastasis: radiobiology and clinical implications[J]. Clin Exp Metastasis, 2018, 35(4):223-236. DOI: 10.1007/s10585-017-9867-5.
[47] Che M, Wang R, Li X, et al. Expanding roles of superoxide dismutases in cell regulation and cancer[J]. Drug Discov Today, 2016, 21(1):143-149. DOI: 10.1016/j.drudis.2015.10.001.
[48] Sibenaller Z A, Welsh J L, Du C, et al. Extracellular superoxide dismutase suppresses hypoxia-inducible factor-1α in pancreatic cancer[J]. Free Radic Biol Med, 2014, 69(3):357-366. DOI: 10.1016/j.freeradbiomed.2014.02.002.
[49] Laukkanen M O. Extracellular superoxide dismutase: growth promoter or tumor suppressor?[J]. Oxid Med Cell Longev, 2016, 20(16):1-9. DOI: 10.1155/2016/3612589.
[50] Griess B, Tom E, Domann F, et al. Extracellular superoxide dismutase and its role in cancer[J]. Free Radic Biol Med, 2017, 11(2):464-479. DOI: 10.1016/j.freeradbiomed.2017.08.013.
[51] Mapuskar K A, Anderson C M, Spitz D R, et al. Utilizing superoxide dismutase mimetics to enhance radiation therapy response while protecting normal tissues[J]. Semin Radiat Oncol, 2019, 29(1):72-80. DOI: 10.1016/j.semradonc.2018.10.005.
[52] Cline J M, Dugan G, Bourland J D, et al. Post-irradiation treatment with a superoxide dismutase mimic, MnTnHex-2-PyP⁵⁺, mitigates radiation injury in the lungs of non-human primates after whole-thorax exposure to ionizing radiation[J]. Antioxidants (Basel), 2018, 7(3):40. DOI: 10.3390/antiox7030040.
[53] Decraene D, Smaers K, Gan D, et al. A synthetic superoxide dismutase/catalase mimetic (EUK-134) inhibits membrane-damage-induced activation of mitogen-activated protein kinase pathways and reduces p53 accumulation in ultraviolet B-exposed primary human keratinocytes[J]. J Invest Dermatol, 2004, 122(2):484-491. DOI: 10.1046/j.0022-202X.2004.22215.x.
[54] Zanoni M, Cortesi M, Zamagni A, et al. The role of mesenchymal stem cells in radiation-induced lung fibrosis[J]. Int J Mol Sci, 2019, 20(16):3876. DOI: 10.3390/ijms20163876.
[55] Wei L, Zhang J, Yang Z L, et al. Extracellular superoxide dismutase increased the therapeutic potential of human mesenchymal stromal cells in radiation pulmonary fibrosis[J]. Cytotherapy, 2017, 19(5):586-602. DOI: 10.1016/j.jcyt.2017.02.359.
[56] Makino J, Ogasawara R, Kamiya T, et al. Royal jelly constituents increase the expression of extracellular superoxide dismutase through histone acetylation in monocytic THP-1 cells[J]. J Nat Prod, 2016, 79(4):1137-1143. DOI: 10.1021/acs.jnatprod.6b00037.
[57] Adachi T, Yamada H, Hara H, et al. Increase of urinary extracellular-superoxide dismutase level correlated with cyclic adenosine monophosphate[J]. FEBS Lett, 1999, 458(3):370-374. DOI: 10.1016/s0014-5793(99)01185-0.