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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Blazevic, Tina Schwaiberger, Andrea V. Schachner, Daniel Dirsch, Verena M. Schreiner, Cornelia E. Heiss, Elke H. Atanasov, Atanas G. Werz, Oliver Grojer, Christoph S. Schaible, Anja M. |
| Description | Author Affiliation: Blazevic T ( From the Department for Pharmacognosy, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria and.) |
| Abstract | We showed previously that the small molecule indirubin-3′-monoxime (I3MO) prevents vascular smooth muscle cell (VSMC) proliferation by selectively inhibiting signal transducer and activator of transcription 3 (STAT3). Looking for the underlying upstream molecular mechanism, we here reveal the important role of reactive oxygen species (ROS) for PDGF-induced STAT3 activation in VSMC. We show that neither NADPH-dependent oxidases (Noxes) nor mitochondria, but rather 12/15-lipoxygenase (12/15-LO) are pivotal ROS sources involved in the redox-regulated signal transduction from PDGFR to STAT3. Accordingly, pharmacological and genetic interference with 12/15-LO activity selectively inhibited PDGF-induced Src activation and STAT3 phosphorylation. I3MO is able to blunt PDGF-induced ROS and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) production, indicating an inhibitory action of I3MO on 12/15-LO and consequently on STAT3. We identify 12/15-LO as a hitherto unrecognized signaling hub in PDGF-triggered STAT3 activation and show for the first time a negative impact of I3MO on 12/15-LO. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 49 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-12-06 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Arachidonate 12-Lipoxygenase Metabolism Arachidonate 15-Lipoxygenase Proto-Oncogene Proteins C-sis STAT3 Transcription Factor Animals Genetics Cell Proliferation Drug Effects Cells, Cultured Indoles Pharmacology Mice Myocytes, Smooth Muscle Cytology Oximes Phosphorylation RNA, Small Interfering Reactive Oxygen Species Receptors, Platelet-Derived Growth Factor Signal Transduction Src-Family Kinases Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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