Inhibition of tumor necrosis factor signal transduction in endothelial cells by dimethylaminopurine Journal Article
| Authors: | Marino, M. W.; Dunbar, J. D.; Wu, L. W.; Ngaiza, J. R.; Han, H. M.; Guo, D.; Matsushita, M.; Nairn, A. C.; Zhang, Y.; Kolesnick, R.; Jaffe, E. A.; Donner, D. B. |
| Article Title: | Inhibition of tumor necrosis factor signal transduction in endothelial cells by dimethylaminopurine |
| Abstract: | Tumor necrosis factor (TNF) promotes diverse responses in endothelial cells that are important to the host response to infections and malignancies; however, less is known of the postreceptor events important to TNF action in endothelial cells than in many other cell types. Since phosphorylation cascades are implicated in cytokine signaling, the effects of the protein kinase inhibitor dimethylaminopurine (DMAP) on TNF action in bovine aortic endothelial cells (BAEC) were investigated. In BAEC, TNF promotes phosphorylation of eukaryotic initiation factor 4E (eIF-4E), c-Jun N-terminal kinase (JNK) and ceramide-activated protein kinase activities, Jun-b expression, prostacyclin production, and, when protein synthesis is inhibited, cytotoxicity. DMAP abrogated or significantly attenuated each of these responses to TNF, without affecting the specific binding of TNF to its receptors. Histamine, another agent active in the endothelium, promotes phosphorylation of elongation factor-2 (EF-2) and prostacyclin production, but not phosphorylation of eIF-4E in BAEC. Histamine-stimulated EF-2 phosphorylation was not inhibited and prostacyclin production was unaffected by DMAP. These observations demonstrate that a distinct signal transduction cascade, which can be selectively inhibited by DMAP, promotes the response of BAEC to TNF. Thus, we have identified a reagent, DMAP, that may be useful for characterizing the TNF signal transduction pathway. |
| Keywords: | signal transduction; protein phosphorylation; nonhuman; animal cell; animals; enzyme inhibition; drug effect; phosphorylation; animalia; endothelium cell; gene expression regulation; tumor necrosis factor-alpha; vascular endothelium; endothelium, vascular; enzyme inhibitors; eukaryota; protein-serine-threonine kinases; cattle; purine derivative; cell interaction; protein kinase; tumor necrosis factor; ceramide; eukaryotic initiation factor-4e; adenine; prostaglandin synthesis; initiation factor; histamine; bovinae; peptide initiation factors; bos taurus; peptide elongation factors; priority journal; article; oncogene c jun; 6 n,n dimethyladenine; peptide elongation factor 2 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 271 |
| Issue: | 45 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1996-11-08 |
| Start Page: | 28624 |
| End Page: | 28629 |
| Language: | English |
| DOI: | 10.1074/jbc.271.45.28624 |
| PUBMED: | 8910494 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work