Proteomic 2D DIGE profiling of human vascular endothelial cells exposed to environmentally relevant concentration of endocrine disruptor PCB153 and physiological concentration of 17β-estradiol.
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. PCB153 is one of the most commonly found polychlorinated biphenyls, and based on epidemiological studies, has been implicated in cardiovascular disease. The endocrine disruptor PCB153 has been reported to bind the estrogen receptor alpha, induce vessel formation, and increase the formation of reactive oxygen species 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 exposed to PCB153 (100 ng/ml) for 24 h. Using 2D DIGE coupled to MALDI-time of flight (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 CI 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 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.
Felty
Quentin
Q
Department of Environmental and Occupational Health, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. Feltyq@fiu.edu
D002478:Cells, Cultured; D052244:Endocrine Disruptors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D020543:Proteome / Q000378:metabolism*; D057825:Two-Dimensional Difference Gel Electrophoresis
D052244:Endocrine Disruptors; D020543:Proteome; D004958:Estradiol; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl