Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Scinderin Promotes Hydrogen Peroxide-induced Lens Epithelial Cell Injury in Age-related Cataract

Author(s): Yan Li, Li Tang*, Guanxing Dang, Mengyuan Ma and Xingfang Tang

Volume 24, Issue 11, 2024

Published on: 01 November, 2023

Page: [1426 - 1436] Pages: 11

DOI: 10.2174/0115665240250050231030110542

Price: $65

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 H2O2 to mimic the oxidative stress in ARC. The role of SCIN was investigated by gain-of-function (overexpression) and loss-offunction (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 H2O2-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 H2O2-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.

« Previous Next »
[1]
Hejtmancik JF, Shiels A. Overview of the Lens. Prog Mol Biol Transl Sci 2015; 134: 119-27.
[http://dx.doi.org/10.1016/bs.pmbts.2015.04.006] [PMID: 26310153]
[2]
Khago D, Bierma JC, Roskamp KW, Kozlyuk N, Martin RW. Protein refractive index increment is determined by conformation as well as composition. J Phys Condens Matter 2018; 30(43): 435101.
[http://dx.doi.org/10.1088/1361-648X/aae000] [PMID: 30280702]
[3]
Avetisov KS, Bakhchieva NA, Avetisov SE, et al. Biomechanical properties of the lens capsule: A review. J Mech Behav Biomed Mater 2020; 103: 103600.
[http://dx.doi.org/10.1016/j.jmbbm.2019.103600] [PMID: 32090929]
[4]
Liu Z, Huang S, Zheng Y, et al. The lens epithelium as a major determinant in the development, maintenance, and regeneration of the crystalline lens. Prog Retin Eye Res 2023; 92: 101112.
[http://dx.doi.org/10.1016/j.preteyeres.2022.101112] [PMID: 36055924]
[5]
Yang H, Cui Y, Tang Y, et al. Cytoprotective role of humanin in lens epithelial cell oxidative stress induced injury. Mol Med Rep 2020; 22(2): 1467-79.
[http://dx.doi.org/10.3892/mmr.2020.11202] [PMID: 32627019]
[6]
Bassnett S, Shi Y, Vrensen GFJM. Biological glass: Structural determinants of eye lens transparency. Philos Trans R Soc Lond B Biol Sci 2011; 366(1568): 1250-64.
[http://dx.doi.org/10.1098/rstb.2010.0302] [PMID: 21402584]
[7]
Fan X, Monnier VM. Protein posttranslational modification (PTM) by glycation: Role in lens aging and age-related cataractogenesis. Exp Eye Res 2021; 210: 108705.
[http://dx.doi.org/10.1016/j.exer.2021.108705] [PMID: 34297945]
[8]
Goutham G, Manikandan R, Beulaja M, et al. A focus on resveratrol and ocular problems, especially cataract: From chemistry to medical uses and clinical relevance. Biomed Pharmacother 2017; 86: 232-41.
[http://dx.doi.org/10.1016/j.biopha.2016.11.141] [PMID: 28006748]
[9]
ten Berge JC, Fazil Z, van den Born LI, et al. Intraocular cytokine profile and autoimmune reactions in retinitis pigmentosa, age‐related macular degeneration, glaucoma and cataract. Acta Ophthalmol 2019; 97(2): 185-92.
[http://dx.doi.org/10.1111/aos.13899] [PMID: 30298670]
[10]
Olson RJ, Braga-Mele R, Chen SH, et al. Cataract in the adult eye preferred practice pattern®. Ophthalmology 2017; 124(2): P1-P119.
[http://dx.doi.org/10.1016/j.ophtha.2016.09.027] [PMID: 27745902]
[11]
Lee CM, Afshari NA. The global state of cataract blindness. Curr Opin Ophthalmol 2017; 28(1): 98-103.
[http://dx.doi.org/10.1097/ICU.0000000000000340] [PMID: 27820750]
[12]
Keel S, He M. Risk factors for age‐related cataract. Clin Exp Ophthalmol 2018; 46(4): 327-8.
[http://dx.doi.org/10.1111/ceo.13309] [PMID: 29898261]
[13]
Shen Q, Zhou T. 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 2021; 22(5): 1286.
[http://dx.doi.org/10.3892/etm.2021.10721] [PMID: 34630641]
[14]
Petrou AL, Terzidaki A. A meta-analysis and review examining a possible role for oxidative stress and singlet oxygen in diverse diseases. Biochem J 2017; 474(16): 2713-31.
[http://dx.doi.org/10.1042/BCJ20161058] [PMID: 28768713]
[15]
Beebe DC, Holekamp NM, Shui YB. Oxidative damage and the prevention of age-related cataracts. Ophthalmic Res 2010; 44(3): 155-65.
[http://dx.doi.org/10.1159/000316481] [PMID: 20829639]
[16]
Smith AJO, Ball SSR, Bowater RP, Wormstone IM. PARP-1 inhibition influences the oxidative stress response of the human lens. Redox Biol 2016; 8: 354-62.
[http://dx.doi.org/10.1016/j.redox.2016.03.003] [PMID: 26990173]
[17]
Ma T, Lan D, He S, et al. Nrf2 protects human lens epithelial cells against H 2 O 2 -induced oxidative and ER stress: The ATF4 may be involved. Exp Eye Res 2018; 169: 28-37.
[http://dx.doi.org/10.1016/j.exer.2018.01.018] [PMID: 29421327]
[18]
Zunino R, Li Q, Rosé SD, et al. Expression of scinderin in megakaryoblastic leukemia cells induces differentiation, maturation, and apoptosis with release of plateletlike particles and inhibits proliferation and tumorigenesis. Blood 2001; 98(7): 2210-9.
[http://dx.doi.org/10.1182/blood.V98.7.2210] [PMID: 11568009]
[19]
Vaysse A, Fang S, Brossard M, et al. A comprehensive genome‐wide analysis of melanoma Breslow thickness identifies interaction between CDC42 and SCIN genetic variants. Int J Cancer 2016; 139(9): 2012-20.
[http://dx.doi.org/10.1002/ijc.30245] [PMID: 27347659]
[20]
Miura N, Takemori N, Kikugawa T, Tanji N, Higashiyama S, Yokoyama M. Adseverin: A novel cisplatin‐resistant marker in the human bladder cancer cell line HT1376 identified by quantitative proteomic analysis. Mol Oncol 2012; 6(3): 311-22.
[http://dx.doi.org/10.1016/j.molonc.2011.12.002] [PMID: 22265592]
[21]
Jian W, Zhang X, Wang J, et al. Scinderin knockdown inhibits proliferation and promotes apoptosis in human breast carcinoma cells. Oncol Lett 2018; 16(3): 3207-14.
[http://dx.doi.org/10.3892/ol.2018.9009] [PMID: 30127916]
[22]
Dong L, Dong B. 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 2021; 22(5): 1323.
[http://dx.doi.org/10.3892/etm.2021.10758] [PMID: 34630677]
[23]
Qi L, Zhou Y, Li W, et al. Effect of Moringa oleifera stem extract on hydrogen peroxide-induced opacity of cultured mouse lens. BMC Complement Altern Med 2019; 19(1): 144.
[http://dx.doi.org/10.1186/s12906-019-2555-z] [PMID: 31226981]
[24]
Qi HP, Wei SQ, Zhang LQ, et al. Preventive effect of danshensu on selenite-induced cataractogenesis in cultured rat lens. Clin Exp Ophthalmol 2013; 41(2): 172-9.
[http://dx.doi.org/10.1111/j.1442-9071.2012.02837.x] [PMID: 22712555]
[25]
Gayathri Devi V, Rooban BN, Sasikala V, Sahasranamam V, Abraham A. Isorhamnetin-3-glucoside alleviates oxidative stress and opacification in selenite cataract in vitro. Toxicol In Vitro 2010; 24(6): 1662-9.
[http://dx.doi.org/10.1016/j.tiv.2010.05.021] [PMID: 20566334]
[26]
Fukuoka H, Afshari NA. The impact of age-related cataract on measures of frailty in an aging global population. Curr Opin Ophthalmol 2017; 28(1): 93-7.
[http://dx.doi.org/10.1097/ICU.0000000000000338] [PMID: 27820747]
[27]
Chirumbolo S. World J Mens Health Oxidative stress, nutrition and cancer: Friends or foes? 2021; 39(1): 19-30.
[http://dx.doi.org/10.5534/wjmh.190167] [PMID: 32202081]
[28]
Chainy GBN, Sahoo DK. Hormones and oxidative stress: An overview. Free Radic Res 2020; 54(1): 1-26.
[http://dx.doi.org/10.1080/10715762.2019.1702656] [PMID: 31868060]
[29]
Wu C, Liu Z, Ma L, et al. MiRNAs regulate oxidative stress related genes via binding to the 3′ UTR and TATA-box regions: A new hypothesis for cataract pathogenesis. BMC Ophthalmol 2017; 17(1): 142.
[http://dx.doi.org/10.1186/s12886-017-0537-9] [PMID: 28806956]
[30]
Shao A, Lin D, Wang L, Tu S, Lenahan C, Zhang J. Oxidative stress at the crossroads of aging, stroke and depression. Aging Dis 2020; 11(6): 1537-66.
[http://dx.doi.org/10.14336/AD.2020.0225] [PMID: 33269106]
[31]
Liu XF, Hao JL, Xie T, et al. Nrf2 as a target for prevention of age-related and diabetic cataracts by against oxidative stress. Aging Cell 2017; 16(5): 934-42.
[http://dx.doi.org/10.1111/acel.12645] [PMID: 28722304]
[32]
Wang Z, Su D, Sun Z, et al. MDM2 phosphorylation mediates H2O2-induced lens epithelial cells apoptosis and age-related cataract. Biochem Biophys Res Commun 2020; 528(1): 112-9.
[http://dx.doi.org/10.1016/j.bbrc.2020.05.060] [PMID: 32471716]
[33]
Hu S, Su D, Sun L, et al. High-expression of ROCK1 modulates the apoptosis of lens epithelial cells in age-related cataracts by targeting p53 gene. Mol Med 2020; 26(1): 124.
[http://dx.doi.org/10.1186/s10020-020-00251-6] [PMID: 33297931]
[34]
Wang Y, Branicky R, Noë A, Hekimi S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol 2018; 217(6): 1915-28.
[http://dx.doi.org/10.1083/jcb.201708007] [PMID: 29669742]
[35]
Dharmajaya R, Sari DK. Malondialdehyde value as radical oxidative marker and endogenous antioxidant value analysis in brain tumor. Ann Med Surg 2022; 77: 103231.
[http://dx.doi.org/10.1016/j.amsu.2021.103231] [PMID: 35638044]
[36]
Chumnarnsilpa S, Robinson RC, Grimes JM, Leyrat C. Calcium-controlled conformational choreography in the N-terminal half of adseverin. Nat Commun 2015; 6(1): 8254.
[http://dx.doi.org/10.1038/ncomms9254] [PMID: 26365202]
[37]
Jia S, Nakaya N, Piatigorsky J. Differential expression patterns and developmental roles of duplicated scinderin-like genes in zebrafish. Dev Dyn 2009; 238(10): 2633-40.
[http://dx.doi.org/10.1002/dvdy.22064] [PMID: 19681161]
[38]
Wang X, Shelton SD, Bordieanu B, et al. Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers. Nature Aging 2022; 2(2): 155-69.
[http://dx.doi.org/10.1038/s43587-021-00164-x] [PMID: 35342888]
[39]
Xu Q, Huff LP, Fujii M, Griendling KK. Redox regulation of the actin cytoskeleton and its role in the vascular system. Free Radic Biol Med 2017; 109: 84-107.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.03.004] [PMID: 28285002]
[40]
Farah ME, Sirotkin V, Haarer B, Kakhniashvili D, Amberg DC. Diverse protective roles of the actin cytoskeleton during oxidative stress. Cytoskeleton 2011; 68(6): 340-54.
[http://dx.doi.org/10.1002/cm.20516] [PMID: 21634027]
[41]
Li J, Qu W, Jiang Y, et al. miR-489 suppresses proliferation and invasion of human bladder cancer cells. Oncol Res 2016; 24(6): 391-8.
[http://dx.doi.org/10.3727/096504016X14666990347518] [PMID: 28281959]
[42]
Jiang R, Zhang C, Gu R, Wu H. MicroRNA-489-3p inhibits neurite growth by regulating PI3K/AKT pathway in spinal cord injury. Pharmazie 2017; 72(5): 272-8.
[PMID: 29441872]
[43]
Song L, Mu L, Wang H. MicroRNA-489-3p aggravates neuronal apoptosis and oxidative stress after cerebral ischemia-reperfusion injury. Bioengineered 2022; 13(6): 14047-56.
[http://dx.doi.org/10.1080/21655979.2022.2062534] [PMID: 35730531]
[44]
Ye Y, Wang P, Zhou F. miR-489-3p inhibits TLR4/NF κB signaling to prevent inflammation in psoriasis. Exp Ther Med 2021; 22(1): 744.
[http://dx.doi.org/10.3892/etm.2021.10176] [PMID: 34055060]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy