Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells Journal Article
| Authors: | Perez-Cruz, I.; Cárcamo, J. M.; Golde, D. W. |
| Article Title: | Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells |
| Abstract: | The FAS receptor-FAS ligand system is a key apoptotic pathway for cells of the immune system. Ligation of the FAS-receptor (CD95) induces apoptosis by activation of pro-caspase-8 followed by downstream events, including an increase in reactive oxygen species (ROS) and the release of proapoptotic factors from the mitochondria, leading to caspase-3 activation. We investigated the role of vitamin C in FAS-mediated apoptosis and found that intracellular accumulation of pharmacologic concentrations of vitamin C inhibited FAS-induced apoptosis in the monocytic U937 cell line and in fresh human monocytes. Cells were loaded with vitamin C by exposure to dehydroascorbic acid (DHA), thereby circumventing in vitro artifacts associated with the poor transport and pro-oxidant effects of ascorbic acid (AA). Vitamin C inhibition of FAS-mediated apoptosis was associated with reduced activity of caspase-3, -8, and -10, as well as diminished levels of ROS and preservation of mitochondrial membrane integrity. Mechanistic studies indicated that the major effect of vitamin C was inhibition of the activation of caspase-8 with no effect on it enzymatic activity. An independent action of high intracellular concentration., of vitamin C on mitochondrial membrane stabilization was also detected. These studies illuminate the nature of redox-dependent signaling in FAS-induced apoptosis of human monocytes and suggest that vitamin C can modulate the immune system by inhibiting FAS-induced monocyte death. © 2003 by The American Society of Hematology. |
| Keywords: | controlled study; human cell; apoptosis; fas antigen; fas ligand; caspase 3; enzyme activation; in vitro study; drug effect; enzyme activity; caspases; immunoregulation; drug accumulation; drug mechanism; reactive oxygen species; reactive oxygen metabolite; caspase 8; ascorbic acid; monocyte; monocytes; mitochondrial membrane; concentration (parameters); mitochondria; drug transport; caspase 10; dehydroascorbic acid; oxidation reduction reaction; cell strain u937; u937 cells; intracellular membranes; membrane stabilization; antigens, cd95; humans; human; priority journal; article |
| Journal Title: | Blood |
| Volume: | 102 |
| Issue: | 1 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2003-07-01 |
| Start Page: | 336 |
| End Page: | 343 |
| Language: | English |
| DOI: | 10.1182/blood-2002-11-3559 |
| PUBMED: | 12623840 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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