OxLDL induced cell death is inhibited by the macrophage synthesised pterin, 7,8-dihydroneopterin, in U937 cells but not THP-1 cells
| Autor: | Sarah K. Baird, Mark B. Hampton, Steven P. Gieseg, Linzi Reid |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Programmed cell death
Macrophage Apoptosis Phosphatidylserines Neopterin Fluorescence Interferon-gamma Cytotoxic T cell Humans Oxidised-low-density-lipoprotein Sulfhydryl Compounds Molecular Biology Caspase Chromatography High Pressure Liquid Analysis of Variance U937 cell biology Chemistry Caspase 3 Macrophages Cell Membrane U937 Cells Cell Biology Atherosclerosis Glutathione Cell biology Lipoproteins LDL Cell culture Caspases biology.protein lipids (amino acids peptides and proteins) Intracellular |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1745(3):361-369 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/j.bbamcr.2005.07.001 |
| Popis: | The atherosclerotic plaque is an inflammatory site where macrophage cells are exposed to cytotoxic oxidised low density lipoprotein (oxLDL). Interferon-γ released from T-cells results in macrophage synthesis of 7,8-dihydroneopterin which has antioxidant and cytoprotective activity. Using the human derived monocyte-like U937 and THP-1 cell lines, we examined whether 7,8-dihydroneopterin could inhibit the cytotoxic effect of oxLDL. In U937 cells, oxLDL caused a dramatic loss of cellular glutathione and caspase independent cell death associated with phosphatidylserine exposure on the plasma membrane. 7,8-Dihydroneopterin completely blocked the cytotoxic effect of oxLDL. In contrast, oxLDL initiated THP-1 cell apoptosis with reduction in cellular thiols, caspase-3 activation and plasma membrane phosphatidylserine exposure. 7,8-Dihydroneopterin was unable to alter these processes or restore the THP-1 cellular thiol content. 7,8-Dihydroneopterin did provide some protection to both THP-1 cells and U937 cells from AAPH derived peroxyl radicals. The preincubation of oxLDL with 7,8-dihydroneopterin did not reduce cytotoxicity, suggesting that 7,8-dihydroneopterin may be acting in U937 cells by scavenging intracellular oxidants generated by the oxLDL. The data show that μM levels of 7,8-dihydroneopterin may prevent oxLDL mediated cellular death within atherosclerotic plaques. |
| Databáze: | OpenAIRE |
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