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Proteomic 2-D DIGE profiling of human vascular endothelial cells exposed to environmentally relevant concentration of endocrine disruptor PCB153 and physiological concentration of 17β-estradiol
| Content Provider | PubMed Central |
|---|---|
| Author | Felty, Quentin |
| Abstract | Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that endocrine disruptors may also contribute to the pathology of cardiovascular disease (CVD). The endocrine disruptor PCB153 has been reported to bind the estrogen receptor, induce vessel formation, and increase the formation of reactive oxygen species (ROS) in endothelial cells. Since PCB153 induced phenotypic changes are similar to estradiol, we postulated that PCB153 activates redox signaling pathways common to 17β-estradiol. Whether the effect of PCB153 on the proteome is comparable to 17β-estradiol is not known. Therefore we investigated the proteome of human microvascular endothelial cells (HMVEC) exposed to PCB153. Using 2-D DIGE coupled to MALDI-TOF/TOF MS, we found 96 protein spots significantly (greater than 1.5 fold) modulated by experimental treatments. Mass spectrometry identified 11 of 13 protein spots with high confidence protein score C.I. that was greater than 95%. Of the identified proteins, lamin A/C and far upstream element-binding protein (FUBP1) were regulated similarly by both treatments. FUBP1 is of particular interest because it controls c-myc. While lamin A/C modulates transcription factor AP-1 function. Interestingly, both c-myc and AP-1 are redox sensitive transcription factors known to regulate genes required for cell growth. Network analysis of these proteins showed transforming growth factor β-1 (TGFB1) and c-myc to play central roles. While our findings do not reveal any mechanisms involved in PCB153 induced vascularization, the identified network does provide a potential target pathway for further mechanistic studies of these relationships. |
| Related Links | http://dx.doi.org/10.1007/s10565-010-9170-6 |
| Ending Page | 68 |
| Page Count | 20 |
| Starting Page | 49 |
| File Format | |
| ISSN | 07422091 |
| e-ISSN | 15736822 |
| Journal | Cell biology and toxicology |
| Issue Number | 1 |
| Volume Number | 27 |
| Language | English |
| Publisher Date | 2011-02-01 |
| Access Restriction | Open |
| Subject Keyword | Toxicology Cell Biology Health, Toxicology and Mutagenesis Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Health, Toxicology and Mutagenesis Toxicology |
