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

Junko Hirata, Ji Ae Ko, Hideki Mochizuki, Kunihiko Funaishi, Ken Yamane, Koh Hei Sonoda, Yoshiaki Kiuchi

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3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalCentral European Journal of Biology
Issue number5
Publication statusPublished - May 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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