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別タイトル
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
著者
平田 潤子
キーワード
Age-related macular degeneration
Retinal pigment epithelium
Oxidative stress
Claudin-1
Tight junction
p38
Mitogen-activated protein kinase
NDC
医学
抄録(英)
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.
言語
英語
NII資源タイプ
学位論文
広大資料タイプ
学位論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
ETD
関連情報(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)
関連情報URL(references)
http://doi.org/10.2478/s11535-014-0287-0
学位記番号
甲第6272号
授与大学
広島大学(Hiroshima University)
学位名
博士(医学)
学位名の英名
Philosophy in Medical Science
学位の種類の英名
doctoral
学位授与年月日
2013-11-28
部局名
医歯薬学総合研究科