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
Rok vydání: 2004
Předmět:
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
Pro tento záznam nejsou dostupné žádné jednotky.