Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival
| العنوان: | Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival |
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| المؤلفون: | Diane E. Handy, Anjali Rai, Edith Lubos, Derrick Kao, Scott R. Oldebeken, Jane A. Leopold, Joseph Loscalzo |
| المصدر: | Molecular and Cellular Biochemistry. 382:153-162 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Cell Survival, medicine.medical_treatment, Clinical Biochemistry, Biology, Article, Dual-specificity phosphatase, medicine, Humans, Viability assay, Extracellular Signal-Regulated MAP Kinases, Molecular Biology, Cell Proliferation, Tumor Necrosis Factor-alpha, Cell growth, Growth factor, NF-kappa B, Endothelial Cells, Cell Biology, General Medicine, NFKB1, Cell biology, Microvessels, biology.protein, Dual-Specificity Phosphatases, Intercellular Signaling Peptides and Proteins, Mitogen-Activated Protein Kinase Phosphatases, Tumor necrosis factor alpha, Signal transduction, Signal Transduction |
| الوصف: | We investigated the effects of tumor necrosis factor-α (TNF-α) exposure on mitogen-activated protein kinase signaling in human microvascular endothelial cells. TNF-α caused a significant suppression of a dual specificity phosphatase, DUSP4, that regulates ERK1/2 activation. Thus, we hypothesized that suppression of DUSP4 enhances cell survival by increasing ERK1/2 signaling in response to growth factor stimulation. In support of this concept, TNF-α pre-exposure increased growth factor-mediated ERK1/2 activation, whereas overexpression of DUSP4 with an adenovirus decreased ERK1/2 compared to an empty adenovirus control. Overexpression of DUSP4 also significantly decreased cell viability, lessened recovery in an in vitro wound healing assay, and decreased DNA synthesis. Pharmacological inhibition of NFκB activation or a dominant negative construct of the inhibitor of κB significantly lessened TNF-α-mediated suppression of DUSP4 expression by 70–84 % and attenuated ERK activation, implicating NFκB-dependent pathways in the TNF-α-mediated suppression of DUSP4 that contributes to ERK1/2 signaling. Taken together, our findings show that DUSP4 attenuates ERK signaling and reduces cell viability, suggesting that the novel crosstalk between NFκB and MAPK pathways contributes to cell survival. |
| تدمد: | 1573-4919 0300-8177 |
| DOI: | 10.1007/s11010-013-1730-7 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2a84f67b573aa504ac5fa39a5d673db https://doi.org/10.1007/s11010-013-1730-7 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a2a84f67b573aa504ac5fa39a5d673db |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15734919 03008177 |
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| DOI: | 10.1007/s11010-013-1730-7 |