Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells
| Autor: | Juan M. Cárcamo, David W. Golde, Isabel Perez-Cruz |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Immunology
Apoptosis Ascorbic Acid Biology Biochemistry Fas ligand Monocytes chemistry.chemical_compound Humans fas Receptor chemistry.chemical_classification Reactive oxygen species Vitamin C U937 cell Cell Biology Hematology Intracellular Membranes U937 Cells Ascorbic acid Fas receptor Dehydroascorbic Acid Cell biology Mitochondria Enzyme Activation chemistry Caspases Dehydroascorbic acid Reactive Oxygen Species |
| Zdroj: | Blood. 102(1) |
| ISSN: | 0006-4971 |
| Popis: | 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 concentrations 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. (Blood. 2003;102:336-343) |
| Databáze: | OpenAIRE |
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