論文

査読有り
2009年

Regulation of 5-Aminolevulinic Acid-Mediated Protoporphyrin IX Accumulation in Human Urothelial Carcinomas

PATHOBIOLOGY
  • Keiji Inoue
  • ,
  • Takashi Karashima
  • ,
  • Masayuki Kamada
  • ,
  • Taro Shuin
  • ,
  • Atsushi Kurabayashi
  • ,
  • Mutsuo Furihata
  • ,
  • Hirofumi Fujita
  • ,
  • Kozo Utsumi
  • ,
  • Junzo Sasaki

76
6
開始ページ
303
終了ページ
314
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1159/000245896
出版者・発行元
KARGER

Purpose: The purpose of this study was to clarify the regulatory mechanism of protoporphyrin IX (PpIX) synthesis mediated by 5-aminolevulinic acid (ALA) in human urothelial carcinoma (UC), leading to improved accuracy in photodynamic diagnosis and therapy using ALA. Experimental Design: PpIX accumulation in cultured UC cells after incubation for 1-5 h with 0.5-5 mM ALA was analyzed by fluorescence analysis using fluorescence microscopy and flow cytometry technique. Results: PpIX fluorescence mediated by ALA was increased, and the intensity of PpIX fluorescence was time-dependently increased in UC cells compared to noncancerous cells. The distribution of endogenous PpIX fluorescence primarily coincided with mitochondria, and then increased at a specific perinuclear region in the cells during the time of incubation. The ALA-mediated PpIX synthesis in UC cells was suppressed by beta-alanine, an inhibitor of beta-transporters of cell membrane, and carbonyl cyanide p -trifluoromethoxy-phenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, the ALA-mediated PpIX accumulation was increased by deferoxamine, an iron chelator, manganese and nitric oxide, which is contributed to PpIX metabolism by inhibiting ferrochelatase activity, generated by a nitric oxide-generating reagent NOC-18. As observed above, ALA-mediated PpIX synthesis in human UC cells was regulated by the process of ALA uptake, ALA conversion to PpIX and metabolism of accumulated PpIX to heme. Conclusions: This shows that the suppression of ferrochelatase increased PpIX accumulation in UC cells using small amount of ALA, thus leading to an improved clinical practicability of photodynamic diagnosis and therapy. Copyright (C) 2009 S. Karger AG, Basel

リンク情報
DOI
https://doi.org/10.1159/000245896
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19955842
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000272330100005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1159/000245896
  • ISSN : 1015-2008
  • PubMed ID : 19955842
  • Web of Science ID : WOS:000272330100005

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