Regulation of 5-aminolevulinic acid-dependent protoporphyrin IX accumulations in human histiocytic lymphoma U937 cells

Yuya Okimura, Hirofumi Fujita, Tetsuya Ogino, Keiji Inoue, Toro Shuin, Hiromi Yano, Tatsuji Yasuda, Masayasu Inoue, Kozo Utsumi, Junzo Sasaki

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The aim of the present work is to clarify the mechanism(s) that regulates the accumulation of protoporphyrin IX (PpIX) in human histiocytic lymphoma cell line U937 incubated with 5-aminolevulinic acid (ALA). Biosynthesis and accumulation of PpIX in the cells was determined after incubation with 0.1 ∼ 5 mM ALA using a flow cytometric technique. The synthesized endogenous PpIX was found to localize predominantly in the mitochondrial region of the cells. The ALA-enhanced PpIX synthesis was suppressed by the presence of either β-alanine, a competitive inhibitor of β-transporters on cell membranes, or carbonyl cyanide p-trifluoromethoxyphenyl hydrazone, an uncoupler of mitochondrial oxidative phosphorylation. In contrast, cellular accumulation of PpIX was enhanced by the presence of either deferoxamine (an iron chelater), MnCl2 (a ferrochelatase inhibitor), or Sn-mesoporphyrin (heme oxygenase inhibitor). These results suggest that ALA-enhanced accumulation of PpIX in U937 cells was regulated by cellular uptake and conversion of ALA to PpIX and by degradation of Heme.

Original languageEnglish
Pages (from-to)69-82
Number of pages14
JournalPhysiological chemistry and physics and medical NMR
Volume39
Issue number1
Publication statusPublished - 2007

Keywords

  • Aminolevulinic acid
  • Ferrochelatase
  • Heme oxygenase-1
  • Protoporphyrin IX
  • β-Transporters

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Physiology
  • Spectroscopy

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