Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro
Апстракт
In our previous experiments, we demonstrated that xylazine, an alpha(2)-adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 muM and 500 muM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 muM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a ...selective alpha-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor Z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells.
Кључне речи:
alpha(2)-adrenergic agonist / apoptosis / signaling / T cell hybridoma / thymocytesИзвор:
Methods and Findings in Experimental and Clinical Pharmacology, 2003, 25, 1, 5-10Издавач:
- Prous Science, Sau-Thomson Reuters, Barcelona
DOI: 10.1358/mf.2003.25.1.772541
ISSN: 0379-0355
PubMed: 12690700
WoS: 000181533700001
Scopus: 2-s2.0-0037223624
Колекције
Институција/група
Fakultet veterinarske medicineTY - JOUR AU - Ćupić, Vitomir AU - Colić, M AU - Jandrić, D. AU - Milojković, B AU - Varagić, Vladislav M. PY - 2003 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/224 AB - In our previous experiments, we demonstrated that xylazine, an alpha(2)-adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 muM and 500 muM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 muM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective alpha-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor Z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells. PB - Prous Science, Sau-Thomson Reuters, Barcelona T2 - Methods and Findings in Experimental and Clinical Pharmacology T1 - Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro VL - 25 IS - 1 SP - 5 EP - 10 DO - 10.1358/mf.2003.25.1.772541 ER -
@article{ author = "Ćupić, Vitomir and Colić, M and Jandrić, D. and Milojković, B and Varagić, Vladislav M.", year = "2003", abstract = "In our previous experiments, we demonstrated that xylazine, an alpha(2)-adrenergic agonist, stimulated proliferation of thymocytes triggered by concanavalin A. In contrast, higher concentrations of xylazine were inhibitory. In this work, we studied the mechanisms involved in immunosuppression of xylazine and found that the compound at concentrations between 100 muM and 500 muM induced apoptosis of rat thymocytes in vitro. In addition, xylazine at concentrations higher than 50 muM also induced apoptosis of a thymocyte hybridoma (BWRT8) and increased apoptosis of the line triggered by T cell receptor (TCR) cross-linking. Apoptosis was confirmed by morphological analysis staining with merocyanine 540 and propidium iodide and in cases of BWRT8 by fragmentation of DNA. The mechanisms of xylazine-induced apoptosis of the BWRT8 hybridoma were further examined. We demonstrated that the process in both nonactivated and activated (TCR cross-linking) BWRT8 cells was not prevented by yohimbine (a selective alpha-adrenergic antagonist) and by antibodies to Fas and Fas-L. In contrast, cell death was completely blocked by a caspase inhibitor Z-Val-Ala-Asp (OMe)-CH2F. Cyclosporine, a calcineurin blocker partly inhibited the xylazine-induced apoptosis of activated BWRT8 cells.", publisher = "Prous Science, Sau-Thomson Reuters, Barcelona", journal = "Methods and Findings in Experimental and Clinical Pharmacology", title = "Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro", volume = "25", number = "1", pages = "5-10", doi = "10.1358/mf.2003.25.1.772541" }
Ćupić, V., Colić, M., Jandrić, D., Milojković, B.,& Varagić, V. M.. (2003). Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro. in Methods and Findings in Experimental and Clinical Pharmacology Prous Science, Sau-Thomson Reuters, Barcelona., 25(1), 5-10. https://doi.org/10.1358/mf.2003.25.1.772541
Ćupić V, Colić M, Jandrić D, Milojković B, Varagić VM. Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro. in Methods and Findings in Experimental and Clinical Pharmacology. 2003;25(1):5-10. doi:10.1358/mf.2003.25.1.772541 .
Ćupić, Vitomir, Colić, M, Jandrić, D., Milojković, B, Varagić, Vladislav M., "Xylazine, an alpha(2)-adrenergic agonist, induces apoptosis of rat thymocytes and a thymocyte hybridoma line in vitro" in Methods and Findings in Experimental and Clinical Pharmacology, 25, no. 1 (2003):5-10, https://doi.org/10.1358/mf.2003.25.1.772541 . .