[1]孙蕾,关丽娜,胡姗姗,等.低氧诱导因子-1α（HIF-1α）在年龄相关性白内障晶状体上皮细胞中的表达[J].眼科新进展,2019,39(6):519-522.[doi:10.13389/j.cnki.rao.2019.0119]
　SUN Lei,GUAN Li-Na,HU Shan-Shan,et al.Expression of hypoxia-inducible factor-1α (HIF-1α) in lens epithelial cells of age-related cataract[J].Recent Advances in Ophthalmology,2019,39(6):519-522.[doi:10.13389/j.cnki.rao.2019.0119]
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低氧诱导因子-1α（HIF-1α）在年龄相关性白内障晶状体上皮细胞中的表达/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
39卷
期数:
2019年6期
页码:
519-522
栏目:
实验研究
出版日期:
2019-06-05

文章信息/Info

Title:
Expression of hypoxia-inducible factor-1α (HIF-1α) in lens epithelial cells of age-related cataract
作者:
孙蕾; 关丽娜; 胡姗姗; 于建渤
157011　黑龙江省牡丹江市，牡丹江医学院病理教研室（孙蕾）；157011　黑龙江省牡丹江市，牡丹江医学院附属红旗医院病理诊断中心，黑龙江省肿瘤疾病防治重点实验室（孙蕾，于建渤）；100086　北京市，国家卫生计生委科学技术研究所（关丽娜）；157011　黑龙江省牡丹江市，牡丹江医学院附属红旗医院眼科（胡姗姗）
Author(s):
SUN Lei; GUAN Li-Na; HU Shan-Shan; YU Jian-Bo
Pathology Teaching and Research Office,Mudanjiang Medical University(SUN Lei),Mudanjiang 157011,Heilongjiang Province,China;Department of Pathology,Mudanjiang Medical University Affiliated Hongqi Hospital,Key Laboratory of Cancer Prevention and Treatment in Heilongjiang Province(SUN Lei,
关键词:
低氧诱导因子-1α; 年龄相关性白内障; 晶状体上皮细胞; 氧化应激; 凋亡
Keywords:
HIF-1α; age-related cataract; lens epithelial cells; oxidative stress; apoptosis
分类号:
R776.1
DOI:
10.13389/j.cnki.rao.2019.0119
文献标志码:
A
摘要:
目的　检测低氧诱导因子-1α（hypoxia inducible factor-1α，HIF-1α）在年龄相关性白内障（age-related cataract，ARC）晶状体上皮细胞（lens epithelial cells，LECs）中的表达情况，并探讨HIF-1α在ARC发生和发展中的作用。方法　建立氧化应激诱导LECs（SRA01/04）凋亡的细胞模型，H2O2浓度为200 μmol·L-1，并设立正常细胞作为对照组，用Western blot方法检测HIF-1α的表达差异；建立自然衰老的白内障小鼠模型（约为18个月龄），并设立青年小鼠作为正常对照组（约8个月龄），用免疫组织化学方法检测小鼠LECs中HIF-1α的表达差异。收集离体的人的前囊膜，术中分离出ARC患者的前囊膜，用免疫组织化学方法检测LECs中HIF-1α表达差异。结果　氧化应激条件下，SRA01/04细胞系HIF-1α蛋白表达降低。随后在体实验验证，与青年小鼠相比，白内障组小鼠LECs中HIF-1α蛋白表达降低。同样的实验结果在ARC患者LECs中得到证实。结论　HIF-1α与ARC相关，HIF-1α的降低可能参与ARC的发生发展。
Abstract:
Objective　To detect the expression of hypoxia-inducible factor-1α (HIF-1α) in lens epithelial cells (LECs) of age-related cataract (ARC) and to explore the role of HIF-1α in the development and progression of ARC.Methods　A cell model of oxidative stress-induced apoptosis of LECs (SRA01/04) was established and the concentration of H2O2 was 200 μmol·L-1.The normal cells were established as a control group.The expression of HIF-1α in two groups was detected by Western blot.A mouse model of natural aging cataract was established (about 18 months old) and young mice were established as a normal control group (about 8 months old).The expression of HIF-1α in mouse LECs was detected by immunohistochemistry.The anterior capsule isolated from ARC patients was collected during operation.The expression of HIF-1α in LECs was detected by immunohistochemistry.Results　The expression of HIF-1α in SRA01/04 cell line was decreased under oxidative stress.Subsequent experiments in vivo demonstrated that HIF-1α expression was decreased in LECs of cataract mice compared with young mice.The same experimental results were confirmed in LECs of ARC patients.Conclusion　The results of this study suggest that HIF-1α is associated with ARC and the decrease of HIF-1α may be involved in the development of ARC.

参考文献/References:

［1］　MICHAEL R,BRON A J.The ageing lens and cataract:a model of normal and pathological ageing［J］.Philos Trans R Soc Lond B Biol Sci,2011,366(1568):1278-1292.
［2］　CHI X X,LIU Y Y,SHI S N,CONG Z,LIANG Y Q,ZHANG H J.XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract:a meta-analysis［J］.Mol Vis,2015,21:335-346.
［3］　WANG S,GUO C,YU M,NING X,YAN B,ZHAO J,et al.Identification of H2O2 induced oxidative stress associated microRNAs in HLE-B3 cells and their clinical relevance to the progression of age-related nuclear cataract［J］.BMC Ophthalmol,2018,18(1):93.
［4］　MAIESE K.New insights for oxidative stress and diabetes mellitus［J］.Oxid Med Cell Longev,2015,2015:1-17.
［5］　KORSAGER L M,MATCHKOV V V.Hypertension and physical exercise:The role of oxidative stress［J］.Medicina,2016,52(1):19-27.
［6］　FRAIKIN G Y.Signaling mechanisms regulating diverse plant cell responses to UVB radiation［J］.Biochemistry,2018,83(7):787-794.
［7］　ZINELLU E,ZINELLU A,FOIS A G,CARRU C,PIRINA P.Circulating biomarkers of oxidative stress in chronic obstructive pulmonary disease:a systematic review［J］.Respir Res,2016,17(1):150.
［8］　ZHU X J,LI D,DU Y,HE W,LU Y.DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes［J］.Redox Biol,2018,19:179-189.
［9］　LU B,CHRISTENSEN I T,MA L,WANG X L,JIANG L F,WANG C X,et al.miR-24-p53 pathway evoked by oxidative stress promotes lens epithelial cell apoptosis in age-related cataracts［J］.Mol Med Rep,2018,17(4):5021-5028.
［10］　SPADARI R C,CAVADAS C,De CARVALHO A E T S,ORTOLANI D,De MOURA A L,VASSALO P F.Role of beta-adrenergic receptors and sirtuin signaling in the heart during aging,heart failure,and adaptation to stress［J］.Cell Mol Neurobiol,2018,38(1):109-120.
［11］　HANDA P,MALIKEN B D,NELSON J E,MORGAN-STEVENSON V,NELSON J E,DHILLON B K,et al.Differences in hepatic expression of iron,inflammation and stress-related genes in patients with nonalcoholic steatohepatitis［J］.Ann Hepatol,2017,16(1):77-85.
［12］　SATO M,HIROSE K,KASHIWAKURA I,AOKI M,KAWAGUCHI H,HATAYAMA Y,et al.LW6,a hypoxia-inducible factor1 inhibitor,selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells［J］.Mol Med Rep,2015,12(3):3462-3468.
［13］　NOGUCHI S,TSUCHIYA Y,HASEGAWA M.Lenticular cytoprotection.Part 1:the role of hypoxia inducible factors-1α and -2α and vascular endothelial growth factor in lens epithelial cell survival in hypoxia［J］.Mol Vis,2013,19(5):1-15.
［14］　SEMENZA G L,WANG G L.A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation［J］.Mol Cell Biol,1992,12(12):5447.
［15］　MIRANDA-CRUZ M M,POOM-LLAMAS J J,GODOY-LUGO J A,ORTIZ R M,GMEZ-JIMNEZ S,ROSAS-RODRíGUEZ J A,et al.Silencing of HIF-1 in WSSV-infected white shrimp:Effect on viral load and antioxidant enzymes［J］.Comp Biochem Physiol C Toxicol Pharmacol,2018,213(1):19-26.
［16］　GARCIA C M,SHUI Y B,KAMATH M,DEVILLAR J,JOHNSON R S,GERBER H P,et al.Thefunction of VEGF-A in lens development:Formation of the hyaloid capillary network and protection against transient nuclear cataracts［J］.Exp Eye Res,2009,88(2):270-276.
［17］　HE C,ZHANG W,LI S,RUAN W,XU J,XIAO F.Edaravone improves septic cardiac function by inducing an HIF-1α/HO-1 pathway［J］.Oxid Med Cell Longev,2018,2018:1-11.
［18］　ZHAO M,TANG S,XIN J,WEI Y,LIU D.Reactive oxygen species induce injury of the intestinal epithelium during hyperoxia［J］.Int J Mol Med,2018,41(1):322-330.
［19］　BALDEA I,TEACOE I,OLTEANU D E,VAIDA-VOIEVOD C,CLICHICI A,SIRBU A,et al.Effects of different hypoxia degrees on endothelial cell cultures-time course study［J］.Mech Ageing Dev,2017,172(1):45-50.
［20］　CHANG M L,CHIU C J,SHANG F,TAYLOR A.High glucose activates ChREBP-mediated HIF-1α and VEGF expression in human RPE cells under normoxia［J］.Adv Exp Med Biol,2014,801(801):609-621.
［21］　NAHOMI R B,NAGARAJ R H.The role of HIF-1α in the TGF-β2-mediated epithelial-to-mesenchymal transition of human lens epithelial cells［J］.J Cell Biochem,2018,119(8):6814-6827.
［22］　LIU L,XIAO W.Notch1 signaling induces epithelial-mesenchymal transition in lens epithelium cells during hypoxia［J］.BMC Ophthalmol,2017,17(1):135.
［23］　CHEN Y,WU Q,MIAO A,JIANG Y,WU X,WANG Z,et al.Effect of HSF4b on age related cataract may through its novel downstream target Hif1α［J］.Biochem Biophys Res Commun,2014,453(3):674-678.
［24］　YUAN X H,FAN Y Y,YANG C R,GAO X R,ZHANG L L,HU Y,et al.Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells［J］.J Steroid Biochem Mol Biol,2016,155(Pt A):104-111.
［25］　XIAO H,WANG X L,QIN L,DONG X X,ZHANG J S,YAN Q C.HIF-1α SUMOylation affects the stability and transcriptional activity of HIF-1α in human lens epithelial cells［J］.Graefes Arch Clin Exp Ophthalmol,2015,253(8):1279-1290.
［26］　HAYASHI R,HAYASHI S,FUKUDA K,SAKAI M,MACHIDA S.Immunolocation of aquaporin 8 in human cataractous lenticular epithelial cells［J］.Biomed Hub,2017,2(3):1.
［27］　RADREAU P,RHODES J D,MITHEN R F,KROON P A,SANDERSON J.Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells［J］.Exp Eye Res,2009,89(6):995-1002.
［28］　HARNED J,FERRELL J,LALL M M,FLEISHER L N,NAGAR S,GORALSKA M,et al.Altered ferritin subunit composition:Change in iron metabolism in lens epithelial cells and downstream effects on glutathione levels and VEGF secretion［J］.Invest Ophthalmol Vis Sci,2010,51(9):4437-4446.
［29］　SHUI Y B,ARBEIT J M,JOHNSON R S,BEEBE D C.HIF-1:An age-dependent regulator of lens cell proliferation［J］.Invest Ophthalmol Vis Sci,2008,49(11):4961-4970.

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备注/Memo

备注/Memo:
国家自然科学基金资助（编号：31601116）；牡丹江市科学技术计划项目（编号：Z2015S0030）；牡丹江医学院研究生创新科研项目（编号：2017YJSCX-10MY）
更新日期/Last Update: 2019-06-05