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title alternative
酸化ストレスによる網膜色素上皮細胞内の接着蛋白質claudin-1の発現変化
creator
Hirata, Junko
subject
Age-related macular degeneration
Retinal pigment epithelium
Oxidative stress
Claudin-1
Tight junction
p38
Mitogen-activated protein kinase
NDC
Medical sciences
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.
language
eng
nii type
Thesis or Dissertation
HU type
Doctoral Theses
DCMI type
text
format
application/pdf
text version
ETD
relation references
Junko Hirata, Ji-Ae Ko, Hideki Mochizuki, Kunihiko Funaishi, Ken Yamane, Koh-Hei Sonoda and Yoshiaki Kiuchi; Oxidative stress regulates expression of claudin-1 in human RPE cells; Central European Journal of Biology, May 2014, Volume 9, Issue 5, pp 461-468 (doi: 10.2478/s11535-014-0287-0)
relation references URL
http://doi.org/10.2478/s11535-014-0287-0
grantid
甲第6272号
degreeGrantor
広島大学(Hiroshima University)
degreename Ja
博士(医学)
degreename En
Philosophy in Medical Science
degreelevel
doctoral
date of granted
2013-11-28
department
Graduate School of Biomedical Science