Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Molecular Medicine
  4. Volume 24, Issue 11
  5. Article
Volume 24, Issue 11
  • ISSN: 1566-5240
  • E-ISSN:

Abstract

Background

Scinderin (SCIN) is a calcium-dependent protein implicated in cell growth and apoptosis by regulating actin cleavage and capping. In this study, we investigated the role of SCIN in hydrogen peroxide-induced lens epithelial cell (LEC) injury related to age-related cataract (ARC).

Methods

Anterior lens capsules from ARC patients were collected to examine SCIN expression levels. Immortalized human LEC cell line SRA01/04 and lens capsules freshly isolated from mice were induced by HO to mimic the oxidative stress in ARC. The role of SCIN was investigated by gain-of-function (overexpression) and loss-of-function (knockdown) experiments. Flow cytometry (FCM) and Western-blot (WB) assays were performed to investigate the effect of SCIN on apoptosis. The oxidative stress (OS) was examined by detecting malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) activity. The interaction between SCIN mRNA and miR-489-3p was predicted by StarBase and miRDB databases and validated by luciferase reporter activity assay.

Results

SCIN was significantly elevated in cataract samples, and the expression levels were positively correlated with the nuclear sclerosis grades. SCIN overexpression promoted OS and apoptosis in HO-induced SRA01/04 cells, while SCIN silencing showed the opposite effect. We further showed that miR-489-3p was a negative regulator of SCIN. miR-489-3p overexpression suppressed apoptosis and OS in HO-induced SRA01/04 cells by targeting SCIN.

Conclusion

Our study identified SCIN as an upregulated gene in ARC, which is negatively regulated by miR-489-3p. Targeting miR-489-3p/SCIN axis could attenuate OS-induced apoptosis in LECs.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmm/10.2174/0115665240250050231030110542
2023-11-01
2024-10-12

  • From This Site

    /content/journals/cmm/10.2174/0115665240250050231030110542
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. HejtmancikJ.F. ShielsA. Overview of the Lens.Prog. Mol. Biol. Transl. Sci.201513411912710.1016/bs.pmbts.2015.04.006 26310153
     [Google Scholar]
  2. KhagoD. BiermaJ.C. RoskampK.W. KozlyukN. MartinR.W. Protein refractive index increment is determined by conformation as well as composition.J. Phys. Condens. Matter2018304343510110.1088/1361‑648X/aae000 30280702
     [Google Scholar]
  3. AvetisovK.S. BakhchievaN.A. AvetisovS.E. Biomechanical properties of the lens capsule: A review.J. Mech. Behav. Biomed. Mater.202010310360010.1016/j.jmbbm.2019.103600 32090929
     [Google Scholar]
  4. LiuZ. HuangS. ZhengY. The lens epithelium as a major determinant in the development, maintenance, and regeneration of the crystalline lens.Prog. Retin. Eye Res.20239210111210.1016/j.preteyeres.2022.101112 36055924
     [Google Scholar]
  5. YangH. CuiY. TangY. Cytoprotective role of humanin in lens epithelial cell oxidative stress induced injury.Mol. Med. Rep.20202221467147910.3892/mmr.2020.11202 32627019
     [Google Scholar]
  6. BassnettS. ShiY. VrensenG.F.J.M. Biological glass: Structural determinants of eye lens transparency.Philos. Trans. R. Soc. Lond. B Biol. Sci.201136615681250126410.1098/rstb.2010.0302 21402584
     [Google Scholar]
  7. FanX. MonnierV.M. Protein posttranslational modification (PTM) by glycation: Role in lens aging and age-related cataractogenesis.Exp. Eye Res.202121010870510.1016/j.exer.2021.108705 34297945
     [Google Scholar]
  8. GouthamG. ManikandanR. BeulajaM. A focus on resveratrol and ocular problems, especially cataract: From chemistry to medical uses and clinical relevance.Biomed. Pharmacother.20178623224110.1016/j.biopha.2016.11.141 28006748
     [Google Scholar]
  9. ten BergeJ.C. FazilZ. van den BornL.I. Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract.Acta Ophthalmol.201997218519210.1111/aos.13899 30298670
     [Google Scholar]
  10. OlsonR.J. Braga-MeleR. ChenS.H. Cataract in the adult eye preferred practice pattern®.Ophthalmology20171242P1P11910.1016/j.ophtha.2016.09.027 27745902
     [Google Scholar]
  11. LeeC.M. AfshariN.A. The global state of cataract blindness.Curr. Opin. Ophthalmol.20172819810310.1097/ICU.0000000000000340 27820750
     [Google Scholar]
  12. KeelS. HeM. Risk factors for age‐related cataract.Clin. Exp. Ophthalmol.201846432732810.1111/ceo.13309 29898261
     [Google Scholar]
  13. ShenQ. ZhouT. Knockdown of lncRNA TUG1 protects lens epithelial cells from oxidative stress induced injury by regulating miR-196a-5p expression in age-related cataracts.Exp. Ther. Med.2021225128610.3892/etm.2021.10721 34630641
     [Google Scholar]
  14. PetrouA.L. TerzidakiA. A meta-analysis and review examining a possible role for oxidative stress and singlet oxygen in diverse diseases.Biochem. J.2017474162713273110.1042/BCJ20161058 28768713
     [Google Scholar]
  15. BeebeD.C. HolekampN.M. ShuiY.B. Oxidative damage and the prevention of age-related cataracts.Ophthalmic Res.201044315516510.1159/000316481 20829639
     [Google Scholar]
  16. SmithA.J.O. BallS.S.R. BowaterR.P. WormstoneI.M. PARP-1 inhibition influences the oxidative stress response of the human lens.Redox Biol.2016835436210.1016/j.redox.2016.03.003 26990173
     [Google Scholar]
  17. MaT. LanD. HeS. Nrf2 protects human lens epithelial cells against H 2 O 2 -induced oxidative and ER stress: The ATF4 may be involved.Exp. Eye Res.2018169283710.1016/j.exer.2018.01.018 29421327
     [Google Scholar]
  18. ZuninoR. LiQ. RoséS.D. Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis.Blood20019872210221910.1182/blood.V98.7.2210 11568009
     [Google Scholar]
  19. VaysseA. FangS. BrossardM. A comprehensive genome‐wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants.Int. J. Cancer201613992012202010.1002/ijc.30245 27347659
     [Google Scholar]
  20. MiuraN. TakemoriN. KikugawaT. TanjiN. HigashiyamaS. YokoyamaM. Adseverin: A novel cisplatin‐resistant marker in the human bladder cancer cell line HT1376 identified by quantitative proteomic analysis.Mol. Oncol.20126331132210.1016/j.molonc.2011.12.002 22265592
     [Google Scholar]
  21. JianW. ZhangX. WangJ. Scinderin knockdown inhibits proliferation and promotes apoptosis in human breast carcinoma cells.Oncol. Lett.20181633207321410.3892/ol.2018.9009 30127916
     [Google Scholar]
  22. DongL. DongB. miR-489-3p overexpression inhibits lipopolysaccharide induced nucleus pulposus cell apoptosis, inflammation and extracellular matrix degradation via targeting Toll like receptor 4.Exp. Ther. Med.2021225132310.3892/etm.2021.10758 34630677
     [Google Scholar]
  23. QiL. ZhouY. LiW. Effect of Moringa oleifera stem extract on hydrogen peroxide-induced opacity of cultured mouse lens.BMC Complement. Altern. Med.201919114410.1186/s12906‑019‑2555‑z 31226981
     [Google Scholar]
  24. QiH.P. WeiS.Q. ZhangL.Q. Preventive effect of danshensu on selenite-induced cataractogenesis in cultured rat lens.Clin. Exp. Ophthalmol.201341217217910.1111/j.1442‑9071.2012.02837.x 22712555
     [Google Scholar]
  25. Gayathri DeviV. RoobanB.N. SasikalaV. SahasranamamV. AbrahamA. Isorhamnetin-3-glucoside alleviates oxidative stress and opacification in selenite cataract in vitro.Toxicol. In Vitro20102461662166910.1016/j.tiv.2010.05.021 20566334
     [Google Scholar]
  26. FukuokaH. AfshariN.A. The impact of age-related cataract on measures of frailty in an aging global population.Curr. Opin. Ophthalmol.2017281939710.1097/ICU.0000000000000338 27820747
     [Google Scholar]
  27. ChirumboloS. World J Mens Health Oxidative stress, nutrition and cancer:Friends or foes?2021391193010.5534/wjmh.19016732202081
     [Google Scholar]
  28. ChainyG.B.N. SahooD.K. Hormones and oxidative stress: An overview.Free Radic. Res.202054112610.1080/10715762.2019.1702656 31868060
     [Google Scholar]
  29. WuC. LiuZ. MaL. MiRNAs regulate oxidative stress related genes via binding to the 3′ UTR and TATA-box regions: A new hypothesis for cataract pathogenesis.BMC Ophthalmol.201717114210.1186/s12886‑017‑0537‑9 28806956
     [Google Scholar]
  30. ShaoA. LinD. WangL. TuS. LenahanC. ZhangJ. Oxidative stress at the crossroads of aging, stroke and depression.Aging Dis.20201161537156610.14336/AD.2020.0225 33269106
     [Google Scholar]
  31. LiuX.F. HaoJ.L. XieT. Nrf2 as a target for prevention of age-related and diabetic cataracts by against oxidative stress.Aging Cell201716593494210.1111/acel.12645 28722304
     [Google Scholar]
  32. WangZ. SuD. SunZ. MDM2 phosphorylation mediates H2O2-induced lens epithelial cells apoptosis and age-related cataract.Biochem. Biophys. Res. Commun.2020528111211910.1016/j.bbrc.2020.05.060 32471716
     [Google Scholar]
  33. HuS. SuD. SunL. High-expression of ROCK1 modulates the apoptosis of lens epithelial cells in age-related cataracts by targeting p53 gene.Mol. Med.202026112410.1186/s10020‑020‑00251‑6 33297931
     [Google Scholar]
  34. WangY. BranickyR. NoëA. HekimiS. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.J. Cell Biol.201821761915192810.1083/jcb.201708007 29669742
     [Google Scholar]
  35. DharmajayaR. SariD.K. Malondialdehyde value as radical oxidative marker and endogenous antioxidant value analysis in brain tumor.Ann. Med. Surg.20227710323110.1016/j.amsu.2021.103231 35638044
     [Google Scholar]
  36. ChumnarnsilpaS. RobinsonR.C. GrimesJ.M. LeyratC. Calcium-controlled conformational choreography in the N-terminal half of adseverin.Nat. Commun.201561825410.1038/ncomms9254 26365202
     [Google Scholar]
  37. JiaS. NakayaN. PiatigorskyJ. Differential expression patterns and developmental roles of duplicated scinderin-like genes in zebrafish.Dev. Dyn.2009238102633264010.1002/dvdy.22064 19681161
     [Google Scholar]
  38. WangX. SheltonS.D. BordieanuB. Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers.Nature. Aging20222215516910.1038/s43587‑021‑00164‑x 35342888
     [Google Scholar]
  39. XuQ. HuffL.P. FujiiM. GriendlingK.K. Redox regulation of the actin cytoskeleton and its role in the vascular system.Free Radic. Biol. Med.20171098410710.1016/j.freeradbiomed.2017.03.004 28285002
     [Google Scholar]
  40. FarahM.E. SirotkinV. HaarerB. KakhniashviliD. AmbergD.C. Diverse protective roles of the actin cytoskeleton during oxidative stress.Cytoskeleton201168634035410.1002/cm.20516 21634027
     [Google Scholar]
  41. LiJ. QuW. JiangY. miR-489 suppresses proliferation and invasion of human bladder cancer cells.Oncol. Res.201624639139810.3727/096504016X14666990347518 28281959
     [Google Scholar]
  42. JiangR. ZhangC. GuR. WuH. MicroRNA-489-3p inhibits neurite growth by regulating PI3K/AKT pathway in spinal cord injury.Pharmazie2017725272278 29441872
     [Google Scholar]
  43. SongL. MuL. WangH. MicroRNA-489-3p aggravates neuronal apoptosis and oxidative stress after cerebral ischemia-reperfusion injury.Bioengineered2022136140471405610.1080/21655979.2022.2062534 35730531
     [Google Scholar]
  44. YeY. WangP. ZhouF. miR-489-3p inhibits TLR4/NF κB signaling to prevent inflammation in psoriasis.Exp. Ther. Med.202122174410.3892/etm.2021.10176 34055060
     [Google Scholar]
/content/journals/cmm/10.2174/0115665240250050231030110542
Loading
Scinderin Promotes Hydrogen Peroxide-induced Lens Epithelial Cell Injury in Age-related Cataract
Current Molecular Medicine 24, 1426 (2024); https://doi.org/10.2174/0115665240250050231030110542
/content/journals/cmm/10.2174/0115665240250050231030110542
/content/journals/cmm/10.2174/0115665240250050231030110542
Loading

Data & Media loading...

  • Article Type: Research Article
Keyword(s): cataract; gene; LECs; miR-489-3p; oxidative stress; SCIN

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test