Nitric oxide mediates kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: A comparison with oxidative burst

Iwao Kurose, Soichiro Miura, Dai Fukumura, Yoshikazu Yonei, Hidetsugu Saito, Shinichiro Tada, Makoto Suematsu, Masaharu Tsuchiya

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The metabolic changes in rat hepatoma cell line, AH70 cells, after coculturing with Kupffer cells were visualized using a silicon-intensified target camera and subsequent processing with a computer-assisted digital imaging processor. In cocultured tumor cells, nonactivated Kupffer cells reduced mitochondrial energization as indicated by the decrease in the fluorescence intensity of rhodamine 123 (Rh123) and induced lipid peroxidation as shown by the dichlorofluorescein (DCF) activation. The reduction in Rh123 could be eliminated by addition of an analogue of L-arginine (NG-monomethyl-L-arginine), suggesting the involvement of nitric oxide (NO·) in the decrease in mitochondrial energization. Superoxide dismutase did not inhibit the reduction in RH123 but significantly inhibited DCF activation. These findings indicate that the latter reaction was mediated by superoxide anion. Two h after the cells were cocultured, propidium iodide-positive, severely injured tumor cells significantly increased in number. This increase was significantly attenuated by addition of NG-monomethyl-L-arginine but not by superoxide dismutase, suggesting that NO· may be greatly involved in Kupffer cell-mediated injury of AH70 cells. In another set of experiments, the culture medium of Kupffer cells caused no significant alteration of Rh123, DCF, and propidium iodide-associated fluorescences in AH70 cells. In addition, ultrastructural observation revealed that the membrane-to-membrane attachment between Kupffer cells and tumor cells occurred within 30 min after coculturing. These results suggest that Kupffer cell-derived NO· release, triggered by the close contact with tumor cells, may induce damage to tumor cells via inhibition of mitochondrial energization.

Original languageEnglish
Pages (from-to)2676-2682
Number of pages7
JournalCancer Research
Volume53
Issue number11
Publication statusPublished - 1993 Jun 1

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Kupffer Cells
Respiratory Burst
Hepatocellular Carcinoma
Nitric Oxide
Rhodamine 123
omega-N-Methylarginine
Propidium
Neoplasms
Superoxide Dismutase
Fluorescence
Membranes
Silicon
Superoxides
Lipid Peroxidation
Culture Media
Arginine
Observation
Cell Line
Wounds and Injuries

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nitric oxide mediates kupffer cell-induced reduction of mitochondrial energization in hepatoma cells : A comparison with oxidative burst. / Kurose, Iwao; Miura, Soichiro; Fukumura, Dai; Yonei, Yoshikazu; Saito, Hidetsugu; Tada, Shinichiro; Suematsu, Makoto; Tsuchiya, Masaharu.

In: Cancer Research, Vol. 53, No. 11, 01.06.1993, p. 2676-2682.

Research output: Contribution to journalArticle

Kurose, I, Miura, S, Fukumura, D, Yonei, Y, Saito, H, Tada, S, Suematsu, M & Tsuchiya, M 1993, 'Nitric oxide mediates kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: A comparison with oxidative burst', Cancer Research, vol. 53, no. 11, pp. 2676-2682.
Kurose, Iwao ; Miura, Soichiro ; Fukumura, Dai ; Yonei, Yoshikazu ; Saito, Hidetsugu ; Tada, Shinichiro ; Suematsu, Makoto ; Tsuchiya, Masaharu. / Nitric oxide mediates kupffer cell-induced reduction of mitochondrial energization in hepatoma cells : A comparison with oxidative burst. In: Cancer Research. 1993 ; Vol. 53, No. 11. pp. 2676-2682.
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