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Oxidative stress regulates expression of claudin-1 in human RPE cells

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  • Published:
Central European Journal of Biology

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.

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Abbreviations

AMD:

age-related macular degeneration

BRB:

blood-retinal barrier

BSA:

bovine serum albumin

ERK:

extracellular signal-regulated kinase

G3PDH:

glyceraldehyde-3-phosphate dehydrogenase

JNK:

c-Jun NH2-terminal kinase

MAPK:

mitogen-activated protein kinase

PBS(-):

Ca2+- and Mg2+-free phosphate-buffered saline

RPE:

retinal pigment epithelium

RT:

reverse transcription

TER:

transepithelial electrical resistance

TJ:

tight junction

ZO-1:

zonula occludens-1

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Authors and Affiliations

  1. Department of Ophthalmology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Minami-Kasumi, Hiroshima City, Hiroshima, 734-8551, Japan

    Junko Hirata, Ji-Ae Ko, Hideki Mochizuki, Kunihiko Funaishi, Ken Yamane & Yoshiaki Kiuchi

  2. Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube City, Yamaguchi, 755-8505, Japan

    Koh-Hei Sonoda

Authors
  1. Junko Hirata
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  2. Ji-Ae Ko
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  3. Hideki Mochizuki
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  4. Kunihiko Funaishi
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  5. Ken Yamane
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  6. Koh-Hei Sonoda
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  7. Yoshiaki Kiuchi
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Correspondence to Ji-Ae Ko.

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Hirata, J., Ko, JA., Mochizuki, H. et al. Oxidative stress regulates expression of claudin-1 in human RPE cells. cent.eur.j.biol. 9, 461–468 (2014). https://doi.org/10.2478/s11535-014-0287-0

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  • DOI: https://doi.org/10.2478/s11535-014-0287-0

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