Role of A20 in cIAP-2 protection against tumor necrosis factor α (TNF-α)-mediated apoptosis in endothelial cells
| Autor: | Xiaoxiao Song, Angela F. Messmer-Blust, Melissa J. Philbrick, Jamal S. Rana, Jian Li, Jiaping Wu, Shuzhen Guo, Jue-Lon Shie |
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| Rok vydání: | 2013 |
| Předmět: |
Gene Expression
Apoptosis cIAP-2 Inhibitor of Apoptosis Proteins lcsh:Chemistry 0302 clinical medicine lcsh:QH301-705.5 Spectroscopy Cells Cultured Phosphoinositide-3 Kinase Inhibitors 0303 health sciences Caspase 3 Reverse Transcriptase Polymerase Chain Reaction Intracellular Signaling Peptides and Proteins Nuclear Proteins General Medicine Baculoviral IAP Repeat-Containing 3 Protein Computer Science Applications Cell biology XIAP Endothelial stem cell DNA-Binding Proteins Vascular endothelial growth factor A A20 030220 oncology & carcinogenesis Tumor necrosis factor alpha RNA Interference Signal Transduction endothelium Morpholines Ubiquitin-Protein Ligases Blotting Western Biology Inhibitor of apoptosis Vascular endothelial growth inhibitor TNF-α apoptosis Catalysis Article Inorganic Chemistry 03 medical and health sciences Animals Humans Physical and Theoretical Chemistry Molecular Biology Tumor Necrosis Factor alpha-Induced Protein 3 030304 developmental biology Dose-Response Relationship Drug Tumor Necrosis Factor-alpha Organic Chemistry Endothelial Cells HEK293 Cells lcsh:Biology (General) lcsh:QD1-999 Chromones Cattle Phosphatidylinositol 3-Kinase |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 15, Iss 3, Pp 3816-3833 (2014) International Journal of Molecular Sciences; Volume 15; Issue 3; Pages: 3816-3833 |
| ISSN: | 1422-0067 |
| Popis: | Tumor necrosis factor α (TNF-α) influences endothelial cell viability by altering the regulatory molecules involved in induction or suppression of apoptosis. However, the underlying mechanisms are still not completely understood. In this study, we demonstrated that A20 (also known as TNFAIP3, tumor necrosis factor α-induced protein 3, and an anti-apoptotic protein) regulates the inhibitor of apoptosis protein-2 (cIAP-2) expression upon TNF-α induction in endothelial cells. Inhibition of A20 expression by its siRNA resulted in attenuating expression of TNF-α-induced cIAP-2, yet not cIAP-1 or XIAP. A20-induced cIAP-2 expression can be blocked by the inhibition of phosphatidyl inositol-3 kinase (PI3-K), but not nuclear factor (NF)-κB, while concomitantly increasing the number of endothelial apoptotic cells and caspase 3 activation. Moreover, TNF-α-mediated induction of apoptosis was enhanced by A20 inhibition, which could be rescued by cIAP-2. Taken together, these results identify A20 as a cytoprotective factor involved in cIAP-2 inhibitory pathway of TNF-α-induced apoptosis. This is consistent with the idea that endothelial cell viability is dependent on interactions between inducers and suppressors of apoptosis, susceptible to modulation by TNF-α. |
| Databáze: | OpenAIRE |
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