Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cancer Res. 1993 Jun 1;53(11):2676-82.

Nitric oxide mediates Kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: a comparison with oxidative burst.

Author information

  • 1Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.

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.

PMID:
8388320
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk