For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
28
references
 Top references
cited by
24
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      244
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      TRIM69 inhibits cataractogenesis by negatively regulating p53

      research-article
      Author(s): a , b , c , d , e , 1 , f , 1 , a , b , c , d , e , a , b , c , d , e , a , b , c , d , e , a , b , c , d , e , ∗
      Publication date (Electronic):
      Journal: Redox Biology
      Publisher: Elsevier
      Keywords: Cataract, TRIM69, p53, UVB, Foxo3a, NHC, National Health Commission, UVB, Ultraviolet B, ROS, reactive oxygen species, HLECs, human lens epithelial cells, TRIM69, tripartite motif 69, Foxo3a, forkhead box protein 3a, Bcl-2, B-cell lymphoma-2, Bax, Bcl-2-associated X protein, DNA, deoxyribonucleic acid, SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, GADPH, glyceraldehyde-3-phosphate dehydrogenase, RPMI, Roswell Park Memorial Institute, PBS, phosphate buffered saline, PFT α, Pifithrin-α, OE, Overexpression, NAC, N-acetyl-l-cysteine, shRNA, Short hairpin RNA, FITC, fluorescein isothiocyanate, PI, propidium iodide, DCFH-DA, 2′,7′-Dichlorodihydrofluorescein diacetate, DHE, dihydroethidium, RIPA, Radio Immunoprecipitation Assay, SD, Standard Deviation, IP, immunoprecipitation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

          Graphical abstract

          Highlights

          • •

            TRIM69 significantly suppressed UVB-induced apoptosis and ROS production.

          • •

            TRIM69 can interact with p53 and induce its ubiquitination.

          • •

            Foxo3a overexpression significantly enhanced TRIM69 promoter activity.

          • •

            The Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: not found
          • Article: not found

          Live or let die: the cell's response to p53.

          Karen H. Vousden, Xin Lu (2002)
          Article 0 comments Cited 624 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Awakening guardian angels: drugging the p53 pathway.

            Christopher Brown, Sonia Lain, Chandra Verma … (2009)
            Currently, around 11 million people are living with a tumour that contains an inactivating mutation of TP53 (the human gene that encodes p53) and another 11 million have tumours in which the p53 pathway is partially abrogated through the inactivation of other signalling or effector components. The p53 pathway is therefore a prime target for new cancer drug development, and several original approaches to drug discovery that could have wide applications to drug development are being used. In one approach, molecules that activate p53 by blocking protein-protein interactions with MDM2 are in early clinical development. Remarkable progress has also been made in the development of p53-binding molecules that can rescue the function of certain p53 mutants. Finally, cell-based assays are being used to discover compounds that exploit the p53 pathway by either seeking targets and compounds that show synthetic lethality with TP53 mutations or by looking for non-genotoxic activators of the p53 response.
            Article 0 comments Cited 266 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress.

              C LeBel, H Ischiropoulos, S Bondy (2015)
              The use of dichlorofluorescin (DCFH) as a measure of reactive oxygen species was studied in aqueous media. Hydrogen peroxide oxidized DCFH to fluorescent dichlorofluorescein (DCF), and the oxidation was amplified by the addition of ferrous iron. Hydrogen peroxide-induced DCF formation in the presence of ferrous iron was completely inhibited by deferoxamine and partially inhibited by ethylenediaminetetraacetic acid, but was augmented by diethylenetriaminepentaacetic acid. Iron-peroxide-induced oxidation of DCFH was partially inhibited by catalase but not by horseradish peroxidase. Nonchelated iron-peroxide oxidation of DCFH was partially inhibited by several hydroxyl radical scavengers, but was independent of the scavenger concentration, and this suggests that free hydroxyl radical is not involved in the oxidation of DCFH in this system. Superoxide anion did not directly oxidize DCFH. Data suggest that H2O2-Fe(2+)-derived oxidant is mainly responsible for the nonenzymatic oxidation of DCFH. In addition, peroxidase alone and oxidants formed during the reduction of H2O2 by peroxidase oxidize DCFH. Since DCFH oxidation may be derived from several reactive intermediates, interpretation of specific reactive oxygen species involved in biological systems should be approached with caution. However, DCFH remains an attractive probe as an overall index of oxidative stress in toxicological phenomena.
              Article 0 comments Cited 144 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Yinghong Ji
                Journal
                Journal ID (nlm-ta): Redox Biol
                Journal ID (iso-abbrev): Redox Biol
                Title: Redox Biology
                Publisher: Elsevier
                ISSN (Electronic): 2213-2317
                Publication date PMC-release: 02 March 2019
                Publication date Collection: April 2019
                Publication date (Electronic): 02 March 2019
                Volume: 22
                Electronic Location Identifier: 101157
                Affiliations
                [a ]Department of Ophthalmology, Eye & ENT Hospital of Fudan University, No. 83 Fenyang Road, Shanghai, 200031, China
                [b ]Eye Institute, Eye & ENT Hospital of Fudan University, No. 83 Fenyang Road, Shanghai, 200031, China
                [c ]National Health Commission (NHC) Key Laboratory of Myopia (Fudan University), No. 83 Fenyang Road, Shanghai, 200031, China
                [d ]Laboratory of Myopia, Chinese Academy of Medical Sciences, No. 83 Fenyang Road, Shanghai, 200031, China
                [e ]Key Laboratory of Visual Impairment and Restoration of Shanghai, No. 83 Fenyang Road, Shanghai, 200031, China
                [f ]Jiangxi Provincial Key Laboratory of Translational Medicine and Oncology, Jiangxi Cancer Hospital, Jiangxi Cancer Center, Nanchang, 330029, China
                Author notes
                [∗ ]Corresponding author. Department of Ophthalmology & Eye Institute, Eye & ENT Hospital of Fudan University, NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, and Key Laboratory of Visual Impairment and Restoration of Shanghai, No. 83 Fenyang Road, Shanghai, 200031, China. yinghong_ji@ 123456163.com
                [1]

                These authors contributed equally to this work.

                Article
                Publisher ID: S2213-2317(18)31230-8 Publisher ID: 101157
                DOI: 10.1016/j.redox.2019.101157
                PMC ID: 6402377
                PubMed ID: 30844644
                SO-VID: a1ec1e34-c560-40b9-8f1e-c6a41384dfdb
                Copyright © © 2019 The Authors
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 15 December 2018
                Date revision received : 17 February 2019
                Date accepted : 1 March 2019
                Categories
                Subject: Research Paper

                Keywords: cataract,trim69,p53,uvb,foxo3a,nhc, national health commission,uvb, ultraviolet b,ros, reactive oxygen species,hlecs, human lens epithelial cells,trim69, tripartite motif 69,foxo3a, forkhead box protein 3a,bcl-2, b-cell lymphoma-2,bax, bcl-2-associated x protein,dna, deoxyribonucleic acid,sds-page, sodium dodecyl sulfate-polyacrylamide gel electrophoresis,gadph, glyceraldehyde-3-phosphate dehydrogenase,rpmi, roswell park memorial institute,pbs, phosphate buffered saline,pft α, pifithrin-α,oe, overexpression,nac, n-acetyl-l-cysteine,shrna, short hairpin rna,fitc, fluorescein isothiocyanate,pi, propidium iodide,dcfh-da, 2′,7′-dichlorodihydrofluorescein diacetate,dhe, dihydroethidium,ripa, radio immunoprecipitation assay,sd, standard deviation,ip, immunoprecipitation
                Data availability:
                Keywords: cataract, trim69, p53, uvb, foxo3a, nhc, national health commission, uvb, ultraviolet b, ros, reactive oxygen species, hlecs, human lens epithelial cells, trim69, tripartite motif 69, foxo3a, forkhead box protein 3a, bcl-2, b-cell lymphoma-2, bax, bcl-2-associated x protein, dna, deoxyribonucleic acid, sds-page, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gadph, glyceraldehyde-3-phosphate dehydrogenase, rpmi, roswell park memorial institute, pbs, phosphate buffered saline, pft α, pifithrin-α, oe, overexpression, nac, n-acetyl-l-cysteine, shrna, short hairpin rna, fitc, fluorescein isothiocyanate, pi, propidium iodide, dcfh-da, 2′,7′-dichlorodihydrofluorescein diacetate, dhe, dihydroethidium, ripa, radio immunoprecipitation assay, sd, standard deviation, ip, immunoprecipitation

                Comments

                Comment on this article

                scite_

                Similar content244

                See all similar

                Cited by24

                See all cited by

                Most referenced authors647

                See all reference authors