Skip to main content

Advertisement

SpringerLink
Log in

Cx43, ZO-1, alpha-catenin and beta-catenin in cataractous lens epithelial cells

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Specimens of the anterior lens capsule with an attached monolayer of lens epithelial cells (LECs) were obtained from patients (n = 52) undergoing cataract surgery. Specimens were divided into three groups based on the type of cataract: nuclear cataract, cortical cataract and posterior subcapsular cataract (PSC). Clear lenses (n = 11) obtained from donor eyes were used as controls. Expression was studied by immunofluorescence, real-time PCR and Western blot. Statistical analysis was done using the student’s t-test. Immunofluorescence results showed punctate localization of Cx43 at the cell boundaries in controls, nuclear cataract and PSC groups. In the cortical cataract group, cytoplasmic pools of Cx43 without any localization at the cell boundaries were observed. Real-time PCR results showed significant up-regulation of Cx43 in nuclear and cortical cataract groups. Western blot results revealed significant increase in protein levels of Cx43 and significant decrease of ZO-1 in all three cataract groups. Protein levels of alpha-catenin were decreased significantly in nuclear and cortical cataract group. There was no significant change in expression of beta-catenin in the cataractous groups. Our findings suggest that ZO-1 and alpha-catenin are important for gap junctions containing Cx43 in the LECs. Alterations in cell junction proteins may play a role during formation of different types of cataract.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Akoyev V, Das S, Jena S, Grauer L and Takemoto DJ 2009 Hypoxia-regulated activity of PKC epsilon in the lens. Invest. Ophthalmol. Vis. Sci. 50 1271–1282

    Article  PubMed  Google Scholar 

  • Akoyev V and Takemoto DJ 2007 ZO-1 is required for protein kinase C gamma-driven disassembly of connexin 43. Cell Signal. 19 958–967

    Google Scholar 

  • Alapure BV, Praveen MR, Gajjar DU, Vasavada AR, Parmar TJ and Arora AI 2012 Matrix metalloproteinase-2 and −9 activities in the human lens epithelial cells and serum of steroid induced posterior subcapsular cataracts. Mol. Vis. 18 64–73

    PubMed  CAS  Google Scholar 

  • Andersson M, Honarvar A, Sjostrand J, Peterson A and Karlsson JO 2003 Decreased caspase-3 activity in human lens epithelium from posterior subcapsular cataracts. Exp. Eye Res. 76 175–182

    Google Scholar 

  • Bagchi M, Katar M, Lewis J and Maisel H 2002 Associated proteins of lens adherens junction. J. Cell Biochem. 86 700–703

    Google Scholar 

  • Bajpai S, Correia J, Feng Y, Figueiredo J, Sun SX, Longmore GD, Suriano G and Wirtz D 2008 {alpha}-Catenin mediates initial E-cadherin-dependent cell-cell recognition and subsequent bond strengthening. Proc. Nat. Acad. Sci. USA 105 18331–18336

    Google Scholar 

  • Bennett TM and Shiels A 2011 A recurrent missense mutation in GJA3 associated with autosomal dominant cataract linked to chromosome 13q. Mol. Vis. 17 2255–2262

    PubMed  CAS  Google Scholar 

  • Boswell BA, Le AC and Musil LS 2009 Upregulation and maintenance of gap junctional communication in lens cells. Exp. Eye Res. 88 919–927

    Google Scholar 

  • Boswell BA, VanSlyke JK and Musil LS 2010 Regulation of lens gap junctions by Transforming Growth Factor beta. Mol. Biol. Cell 21 1686–1697

    Google Scholar 

  • Chong CC, Stump RJ, Lovicu FJ and McAvoy JW 2009 TGFbeta promotes Wnt expression during cataract development. Exp. Eye Res. 88 307–313

  • Denker BM, Saha C, Khawaja S and Nigam SK 1996 Involvement of a heterotrimeric G protein alpha subunit in tight junction biogenesis. J. Biol. Chem. 271 25750–25753

    Article  PubMed  CAS  Google Scholar 

  • DeRosa AM, Mese G, Li L, Sellitto C, Brink PR, Gong X and White TW 2009 The cataract causing Cx50-S50P mutant inhibits Cx43 and intercellular communication in the lens epithelium. Exp. Eye Res. 315 1063–1075

    Google Scholar 

  • Eldred JA, Dawes LJ and Wormstone IM 2011 The lens as a model for fibrotic disease. Philos. Trans. R. Soc. London B Biol. Sci. 366 1301–1319

    Google Scholar 

  • Eshaghian J and Streeten BW 1980 Human posterior subcapsular cataract. An ultrastructural study of the posteriorly migrating cells. Arch. Ophthalmol. 98 134–143

    Article  PubMed  CAS  Google Scholar 

  • Fanning AS, Jameson BJ, Jesaitis LA and Anderson JM 1998 The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J. Biol. Chem. 273 29745–29753

    Article  PubMed  CAS  Google Scholar 

  • Gao Y and Spray DC 1998 Structural changes in lenses of mice lacking the gap junction protein connexin43. Invest. Ophthalmol. Vis. Sci. 39 1198–1209

    PubMed  CAS  Google Scholar 

  • Govindarajan R, Zhao S, Song XH, Guo RJ, Wheelock M, Johnson KR and Mehta PP 2002 Impaired trafficking of connexins in androgen-independent human prostate cancer cell lines and its mitigation by alpha-catenin. J. Biol. Chem. 277 50087–50097

    Article  PubMed  CAS  Google Scholar 

  • Harris AL 2001 Emerging issues of connexin channels: biophysics fills the gap. Q. Rev. Biophys. 34 325–472

    PubMed  CAS  Google Scholar 

  • He W, Li X, Chen J, Xu L, Zhang F, Dai Q, Cui H, Wang DM, et al. 2011 Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract. Ophthal. Genet. 32 48–53

    Article  PubMed  Google Scholar 

  • Khurana AK and Khurana I 2007 Anatomy and physiology of the eye. 2nd Edition. CBS Publisher & Distributors P Ltd Delhi (India)

  • Kistler J, Christie D and Bullivant S 1988 Homologies between gap junction proteins in lens, heart and liver. Nature 331 721–723

    Article  PubMed  CAS  Google Scholar 

  • Laing JG, Chou BC and Steinberg TH 2005 ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic cells. J. Cell Sci. 118 2167–2176

    Google Scholar 

  • Lin D, Boyle DL and Takemoto DJ 2003 IGF-I-induced phosphorylation of connexin 43 by PKCgamma: regulation of gap junctions in rabbit lens epithelial cells. Invest. Ophthalmol. Vis. Sci. 44 1160–1168

    Article  PubMed  Google Scholar 

  • Long AC, Bomser JA, Grzybowski DM and Chandler HL 2010 All-trans retinoic Acid regulates cx43 expression, gap junction communication and differentiation in primary lens epithelial cells. Curr. Eye Res. 35 670–679

    Google Scholar 

  • Long AC, Colitz CM and Bomser JA 2004 Apoptotic and necrotic mechanisms of stress-induced human lens epithelial cell death. Exp. Biol. Med. 229 1072–1080

    CAS  Google Scholar 

  • Long AC, Colitz CM and Bomser JA 2007 Regulation of gap junction intercellular communication in primary canine lens epithelial cells: role of protein kinase C. Curr. Eye Res. 32 223–231

    Google Scholar 

  • Martinez G, Wijesinghe M, Turner K, Abud HE, Taketo MM, Noda T, Robinson ML and de Iongh RU 2009 Conditional mutations of beta-catenin and APC reveal roles for canonical Wnt signaling in lens differentiation. Invest. Ophthalmol. Vis. Sci. 50 4794–4806

    Article  PubMed  Google Scholar 

  • Meng W and Takeichi M 2009 Adherens junction: molecular architecture and regulation. Cold Spring Harb. Perspect. Biol. 1 a002899

    Google Scholar 

  • Musil LS, Beyer EC and Goodenough DA 1990 Expression of the gap junction protein connexin43 in embryonic chick lens: molecular cloning, ultrastructural localization, and post-translational phosphorylation. J. Membr. Biol. 116 163–175

    Article  PubMed  CAS  Google Scholar 

  • Pizzuti D, Bortolami M, Mazzon E, Buda A, Guariso G, D'Odorico A, Chiarelli S, D’Inca R, et al. 2004 Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet. Digest. Liver Dis. 36 337–341

    Google Scholar 

  • Rhett JM, Jourdan J and Gourdie RG 2011 Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1. Mol. Biol. Cell 22 1516–1528

    Google Scholar 

  • Rochtchina E, Mitchell P, Coroneo M, Wang JJ and Cumming RG 2001 Lower nasal distribution of cortical cataract: the Blue Mountains Eye Study. Clin. Exp. Ophthalmol. 29 111–115

    Article  CAS  Google Scholar 

  • Rungger-Brandle E, Conti A, Leuenberger PM and Rungger D 2005 Expression of alphasmooth muscle actin in lens epithelia from human donors and cataract patients. Exp. Eye Res. 81 539–550

    Google Scholar 

  • Schein OD, West S, Munoz B, Vitale S, Maguire M, Taylor HR and Bressler NM 1994 Cortical lenticular opacification: distribution and location in a longitudinal study. Invest. Ophthalmol. Vis. Sci. 35 363–366

    PubMed  CAS  Google Scholar 

  • Smith AN, Miller LA, Song N, Taketo MM and Lang RA 2005 The duality of beta-catenin function: a requirement in lens morphogenesis and signaling suppression of lens fate in periocular ectoderm. Dev. Biol. 285 477–489

    Article  PubMed  CAS  Google Scholar 

  • Streeten BW and Eshaghian J 1978 Human posterior subcapsular cataract. A gross and flat preparation study. Arch. Ophthalmol. 96 1653–1658

    Article  PubMed  CAS  Google Scholar 

  • Truscott RJ 2005 Age-related nuclear cataract-oxidation is the key. Exp. Eye Res. 80 709–725

    Google Scholar 

  • Tsukita S, Katsuno T, Yamazaki Y, Umeda K and Tamura A 2009 Roles of ZO-1 and ZO-2 in establishment of the belt-like adherens and tight junctions with paracellular permselective barrier function. Ann. NY Acad. Sci. 1165 44–52

    Google Scholar 

  • Vrensen GF 2009 Early cortical lens opacities: a short overview. Acta Ophthalmol. 87 602–610

    Google Scholar 

  • Wagner LM, Saleh SM, Boyle DJ and Takemoto DJ 2002 Effect of protein kinase C gamma on gap junction disassembly in lens epithelial cells and retinal cells in culture. Mol. Vis. 8 59–66

    PubMed  CAS  Google Scholar 

  • Wang L, Luo Y, Wen W, Zhang S and Lu Y 2011 Another evidence for a D47N mutation in GJA8 associated with autosomal dominant congenital cataract. Mol. Vis. 17 2380–2385

    PubMed  CAS  Google Scholar 

  • Wu D, Zhao J and Zhang J 2011 Ultraviolet A exposure induces reversible disruption of gap junction intercellular communication in lens epithelial cells. Int. J. Mol. Med. 28 239–245

    PubMed  CAS  Google Scholar 

  • Wu JC, Tsai RY and Chung TH 2003 Role of catenins in the development of gap junctions in rat cardiomyocytes. J. Cell Biochem. 88 823–835

    Google Scholar 

  • Zhou J, Leonard M, Van Bockstaele E and Menko AS 2007 Mechanism of Src kinase induction of cortical cataract following exposure to stress: destabilization of cell-cell junctions. Mol. Vis. 13 1298–1310

    PubMed  CAS  Google Scholar 

  • Zigman S, Datiles M and Torczynski E 1979 Sunlight and human cataracts. Invest. Ophthalmol. Vis. Sci. 18 462–467

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Anshul Arora is a recipient of the Senior Research Fellowship (SRF) and is thankful to Indian Council of Medical Research (ICMR) for the same. The work was partly supported by Council of Scientific and Industrial Research (CSIR) grant no. 27(01840)/08/EMR-II.

Author information

Authors and Affiliations

  1. Iladevi Cataract and IOL Research Centre, Gurukul Road, Memnagar, Ahmedabad, 380 052, India

    Anshul I Arora, Kaid Johar, Devarshi U Gajjar, Darshini A Ganatra, Forum B Kayastha, Anuradha K Pal, Alpesh R Patel, S Rajkumar & Abhay R Vasavada

Authors
  1. Anshul I Arora
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kaid Johar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Devarshi U Gajjar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Darshini A Ganatra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Forum B Kayastha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anuradha K Pal
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alpesh R Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Rajkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Abhay R Vasavada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abhay R Vasavada.

Additional information

Corresponding editor: Durgadas P Kasbekar

Paper presented in part at the Indian Eye Research Group (IERG) Meeting, Hyderabad, India, July, 2011.

[Arora AI, Johar K, Gajjar DU, Ganatra DA, Kayastha FB, Pal AK, Patel AR, Rajkumar S and Vasavada AR 2012 Cx43, ZO-1, alpha-catenin and beta-catenin in cataractous lens epithelial cells. J. Biosci. 37 1–9] DOI 10.1007/s12038-012-9264-9

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arora, A.I., Johar, K., Gajjar, D.U. et al. Cx43, ZO-1, alpha-catenin and beta-catenin in cataractous lens epithelial cells. J Biosci 37 (Suppl 1), 979–987 (2012). https://doi.org/10.1007/s12038-012-9264-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-012-9264-9

Keywords

Search

Navigation