Abstract
Age-related macular degeneration (AMD) is a neurodegenerative disease associated with irreversible loss of central vision in the elderly. Disruption of the homeostatic function of the retinal pigment epithelium (RPE) is thought to be fundamental to AMD pathogenesis, and oxidative stress is implicated in the associated RPE damage. We examined the effects of oxidative stress on the expression of junctional proteins in cultured human retinal pigment epithelial (ARPE-19) cells. Reverse transcription-PCR and immunoblot analyses revealed that expression of the tight-junction protein claudin-1 was increased at both the mRNA and protein levels 8 to 12 h after exposure of ARPE-19 cells to H2O2, whereas that of the tight-junction protein ZO-1 or the adherens-junction protein N-cadherin was unaffected. Expression of both claudin-1 and N-cadherin was down-regulated by exposure of the cells to H2O2 for longer periods (24 to 48 h). Oxidative stress also induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) with a time course similar to that apparent for the up-regulation of claudin-1 expression. Furthermore, the increase in the abundance of claudin-1 induced by H2O2 was blocked by the p38 inhibitor SB203580. Phosphorylation of the MAPKs ERK and JNK was not affected by H2O2. Our results suggest that modulation of claudin-1 expression in the RPE by oxidative stress may contribute to the pathogenesis of AMD.
[1] The Eye Diseases Prevalence Research Group, Causes and prevalence of visual impairment among adults in the United States, Arch. Ophthalmol., 2004, 122, 477–485 http://dx.doi.org/10.1001/archopht.122.4.47710.1001/archopht.122.4.477Search in Google Scholar
[2] Roth F., Bindewald A., Holz F.G., Key pathophysiologic pathways in age-related macular disease, Graefes Arch. Clin. Exp. Ophthalmol., 2004, 242, 710–716 http://dx.doi.org/10.1007/s00417-004-0976-x10.1007/s00417-004-0976-xSearch in Google Scholar
[3] Rizzolo L.J., Polarity and the development of the outer blood-retinal barrier, Histol. Histopathol., 1997, 12, 1057–1067 Search in Google Scholar
[4] Hamdi H.K., Kenney C., Age-related macular degeneration: a new viewpoint, Front. Biosci., 1994, 8, 255–262 Search in Google Scholar
[5] Zarbin M.A., Current concepts in the pathogenesis of age-related macular degeneration, Arch. Ophthalmol., 2004, 122, 598–614 http://dx.doi.org/10.1001/archopht.122.4.59810.1001/archopht.122.4.598Search in Google Scholar
[6] Strauss O., The retinal pigment epithelium in visual function, Physiol. Rev., 2005, 85, 845–881 http://dx.doi.org/10.1152/physrev.00021.200410.1152/physrev.00021.2004Search in Google Scholar
[7] Smith W., Assink J., Klein R., Mitchell P., Klaver C.C., Klein B.E., et al., Risk factors for age-related macular degeneration: pooled findings from three continents, Ophthalmol., 2001, 108, 697–704 http://dx.doi.org/10.1016/S0161-6420(00)00580-710.1016/S0161-6420(00)00580-7Search in Google Scholar
[8] Cai J., Nelson K.C., Wu M., Sternberg P. Jr., Jones D.P., Oxidative damage and protection of the RPE, Prog. Retin. Eye Res., 2000, 19, 205–221 http://dx.doi.org/10.1016/S1350-9462(99)00009-910.1016/S1350-9462(99)00009-9Search in Google Scholar
[9] Winkler B.S., Boulton M.E., Gottsch J.D., Sternberg P., Oxidative damage and age-related macular degeneration, Mol. Vis., 1999, 5, 32–42 Search in Google Scholar
[10] Jin M., Barron E., He S., Ryan S.J., Hinton D.R., Regulation of RPE intercellular junction integrity and function by hepatocyte growth factor, Invest. Ophthalmol. Vis. Sci., 2002, 43, 2782–2790 Search in Google Scholar
[11] Kerendian J., Enomoto H., Wong C.D., Induction of stress proteins in SV-40 transformed human RPEderived cells by organic oxidants, Curr. Eye Res., 1992, 11, 385–396 http://dx.doi.org/10.3109/0271368920900179210.3109/02713689209001792Search in Google Scholar PubMed
[12] Wong C.G., Lin N.G., Induction of stress proteins in cultured human RPE-derived cells, Curr. Eye Res., 1989, 8, 537–545 http://dx.doi.org/10.3109/0271368890899575110.3109/02713688908995751Search in Google Scholar PubMed
[13] Hackett S.F., Schoenfeld C.L., Freund J., Gottsch J.D., Bhargave S., Campochiaro P.A., Neurotrophic factors, cytokines and stress increase expression of basic fibroblast growth factor in retinal pigmented epithelial cells, Exp. Eye Res., 1997, 64, 865–873 http://dx.doi.org/10.1006/exer.1996.025610.1006/exer.1996.0256Search in Google Scholar PubMed
[14] Alizadeh M., Wada M., Gelfman C.M., Handa J.T., Hjelmeland L.M., Downregulation of differentiation specific gene expression by oxidative stress in ARPE-19 cells, Invest. Ophthalmol. Vis. Sci., 2001, 42, 2706–2713 Search in Google Scholar
[15] Mckay B.S., Irving P.E., Skumatz C.M.B., Burke J.M., Cell-cell adhesion molecules and the development of an epithelial phenotype in cultured human retinal pigment epithelial cells, Exp. Eye Res., 1997, 65, 661–671 http://dx.doi.org/10.1006/exer.1997.037410.1006/exer.1997.0374Search in Google Scholar PubMed
[16] Ko J.A., Yanai R., Morishige N., Takezawa T., Nishida T., Upregulation of connexin43 expression in corneal fibroblasts by corneal epithelial cells, Invest. Ophthalmol. Vis. Sci., 2009, 50, 2054–2060 http://dx.doi.org/10.1167/iovs.08-241810.1167/iovs.08-2418Search in Google Scholar
[17] Yanai R., Ko J.A., Nomi N., Morishige N., Chikama T., Hattori A., et al., Upregulation of ZO-1 in cultured human corneal epithelial cells by a peptide (PHSRN) corresponding to the second cell-binding site of fibronectin, Invest. Ophthalmol. Vis. Sci., 2009, 50, 2757–2764 http://dx.doi.org/10.1167/iovs.08-234110.1167/iovs.08-2341Search in Google Scholar
[18] Villarroel M., Garcia-Ramirez M., Corraliza L., Hernandez C., Simo R., Effects of high glucose concentration on the barrier function and the expression of tight junction proteins in human retinal pigment epithelial cells, Exp. Eye Res., 2009, 89, 913–920 http://dx.doi.org/10.1016/j.exer.2009.07.01710.1016/j.exer.2009.07.017Search in Google Scholar
[19] Campa C., Harding S.P., Anti-VEGF compounds in the treatment of neovascular age related macular degeneration, Curr. Drug Targets, 2011, 12, 173–181 http://dx.doi.org/10.2174/13894501179418267410.2174/138945011794182674Search in Google Scholar
[20] Calabrese A., Bermard J.B., Hoffart L., Faure G., Barouch F., Conrath J., et al., Wet versus dry age-related macular degeneration in patients with central field loss: different effects on maximum reading speed, Invest. Ophthalmol. Vis. Sci., 2011, 52, 2417–2424 http://dx.doi.org/10.1167/iovs.09-505610.1167/iovs.09-5056Search in Google Scholar
[21] Gonzalez-Mariscal L., Betanzos A., Nava P., Jaramillo B.E., Tight junction proteins, Prog. Biophys. Mol. Biol., 2003, 81, 1–44 http://dx.doi.org/10.1016/S0079-6107(02)00037-810.1016/S0079-6107(02)00037-8Search in Google Scholar
[22] Miura Y., Roider J., Triamcinolone acetonide prevents oxidative stress-induced tight junction disruption of retinal pigment epithelial cells, Graefes Arch. Clin. Exp. Ophthalmol., 2009, 247, 641–649 http://dx.doi.org/10.1007/s00417-009-1041-610.1007/s00417-009-1041-6Search in Google Scholar PubMed
[23] Ho T.C., Yang Y.C., Cheng H.C., Wu A.C., Chen S.L., Tsao Y.P., Pigment epithelium-derived factor protects retinal pigment epithelium from oxidantmediated barrier dysfunction, Biochem. Biophys. Res. Commun., 2006, 342, 372–378 http://dx.doi.org/10.1016/j.bbrc.2006.01.16410.1016/j.bbrc.2006.01.164Search in Google Scholar PubMed
[24] Geiger R.C., Waters C.M., Kamp D.W., Glucksberg M.R., KGF prevents oxygen-mediated damage in ARPE-19 cells, Invest. Ophthalmol. Vis. Sci., 2005, 46, 3435–3442 http://dx.doi.org/10.1167/iovs.04-148710.1167/iovs.04-1487Search in Google Scholar PubMed
[25] Bai L., Yan H.H., Zhang D.X., Wang J.M., Sun N.X., Effects of oxidative stress on barrier function of human retina pigment epithelium and its molecular mechanisms, Zhonghua Yan Ke Za Zhi, 2012, 48, 417–422 Search in Google Scholar
[26] Chang L., Karin M., Mammalian MAP kinase signaling cascades, Nature, 2001, 410, 37–40 http://dx.doi.org/10.1038/3506500010.1038/35065000Search in Google Scholar PubMed
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