Regulation of 5-aminolevulinic acid-dependent protoporphyrin IX accumulations in human histiocytic lymphoma U937 cells.
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 beta-alanine, a competitive inhibitor of beta-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.
Okimura
Yuya
Y
Department of Cytology & Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama, Okayama 700-8558, Japan.
Fujita
Hirofumi
H
Ogino
Tetsuya
T
Inoue
Keiji
K
Shuin
Toro
T
Yano
Hiromi
H
Yasuda
Tatsuji
T
Inoue
Masayasu
M
Utsumi
Kozo
K
Sasaki
Junzo
J
D000622:Aminolevulinic Acid / Q000378:metabolism*; D002712:Chlorides; D003676:Deferoxamine; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology*; D017895:Manganese Compounds; D008652:Mesoporphyrins; D011524:Protoporphyrins / Q000378:metabolism*; D020298:U937 Cells
D002712:Chlorides; D017895:Manganese Compounds; D008652:Mesoporphyrins; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D003676:Deferoxamine; C025340:manganese chloride