Photochemically induced increase in endothelial permeablity regulated by RhoA activation

Hiroki Ota, Mimiko Matsumura, Norihisa Miki, Haruyuki Minamitami

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Photochemical reactions used in photodynamic therapy are reported to damage normal cells and tissues in ways that increase endothelial permeability and thereby cause excessive neointimal formation and subsequent restenosis. To investigate the mechanisms of this permeability increase in vitro, human umbilical vein endothelial cells were incubated with the porphyrin precursor δ-aminolevulinic acid and then irradiated with a 646 nm light-emitting diode (LED). Results using Transwells® supports showed that the photochemical reaction increased endothelial permeability by 200%, and fluorescence microscopy revealed that destruction of the capillary-like structures due to cell shrinkage was accompanied by VE-cadherin mislocalization and stress fiber formation. The generated gaps between cells were observed using dyed β1-integrin and total internal reflection fluorescence microscopy. Western blotting indicated that the photochemical reaction phosphorylated GDP-RhoA to GTP-RhoA, a protein that promotes stress fiber formation and inhibits VE-cadherin production. When forskolin/rolipram or 8CPT-2′O-Me- cAMP, both of which inhibit further reaction of phosphorylated RhoA, were added, no formation of stress fibers or mislocalization of VE-cadherin was observed, thus preventing an increase in endothelial permeability. Taken together, photochemically induced RhoA activation appears to play a key role in increasing endothelial permeability during changes in morphology of endothelial cells.

本文言語English
ページ(範囲)1401-1407
ページ数7
ジャーナルPhotochemical and Photobiological Sciences
8
10
DOI
出版ステータスPublished - 2009 1 1

ASJC Scopus subject areas

  • 物理化学および理論化学

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