Overexpression of 15-Lipoxygenase in the Vascular Endothelium Is Associated with Increased Thymic Apoptosis in LDL Receptor-Deficient Mice
Autor: | M. Deutsch, Gad Keren, Jacob George, N. Zurgil, Y Bar-Dayan, Iris Goldberg, Arnon Afek, J. Kopolovich, Sylvie Polak-Charcon, Dror Harats |
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Rok vydání: | 2004 |
Předmět: |
T-Lymphocytes
Clonal Deletion Apoptosis Mice Transgenic Thymus Gland Cysteine Proteinase Inhibitors Antioxidants Pathology and Forensic Medicine Mice Lipoxygenase Deficient mouse Animals Arachidonate 15-Lipoxygenase Humans Molecular Biology Cells Cultured Mice Knockout chemistry.chemical_classification biology Caspase 3 Cell Biology General Medicine Caspase Inhibitors Molecular biology Acetylcysteine Mice Inbred C57BL Vascular endothelium Enzyme Receptors LDL chemistry Biochemistry LDL receptor biology.protein Endothelium Vascular Oligopeptides |
Zdroj: | Pathobiology. 71:261-266 |
ISSN: | 1423-0291 1015-2008 |
DOI: | 10.1159/000080060 |
Popis: | Background: 15-Lipoxygenase (15-LO) is a nonheme iron-containing enzyme that catalyzes the peroxidation of fatty acids. Herein, we studied the effect of 15-LO overexpression in the vascular endothelium on thymocyte apoptosis by evaluating thymuses from low-density lipoprotein receptor-deficient (LDL-RD) mice and LDL-RD/15-LO mice. Thymuses were evaluated by immunhistochemistry and by TUNEL whereas in vitro studies were carried out by employing freshly isolated thymocytes from the respective mice and evaluation of apoptosis by propidium iodide and annexin V cytometry. Methods and Results: The apoptotic index in LDL-RD/15-LO mice was significantly higher than in the LDL-RD mice. In the thymic medulla the difference was smaller, although still significant. Freshly isolated thymus cells from LDL-RD/15-LO mice exhibited a higher rate of spontaneous cell death than controls. Incubation of thymus cells in the presence of the cell-permeable caspase-3 inhibitor DEVD-CMK resulted in a decrease in the frequency of apoptotic cells in LDL-RD/15-LO thymocytes, whereas no effect was evident in control thymocytes. The antioxidant N-acetylcysteine causes the increase in apoptosis in both groups. Conclusion: LDL-RD/15-LO mice exhibit increased thymocyte apoptosis both in vivo and in vitro. These findings may suggest a role for 15-LO in the natural selection of thymocytes. |
Databáze: | OpenAIRE |
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