scholarly journals Assessment of the Effects of Bisphenol A on Dopamine Synthesis and Blood Vessels in the Goldfish Brain

2019 ◽  
Vol 20 (24) ◽  
pp. 6206 ◽  
Author(s):  
Qing Wang ◽  
Fangmei Lin ◽  
Qi He ◽  
Xiaochun Liu ◽  
Shiqiang Xiao ◽  
...  

Bisphenol A (BPA) is an abundant contaminant found in aquatic environments. While a large number of toxicological studies have investigated the effects of BPA, the potential effects of BPA exposure on fish brain have rarely been studied. To understand how BPA impacts goldfish brains, we performed a transcriptome analysis of goldfish brains that had been exposed to 50 μg L−1 and 0 μg L−1 BPA for 30 days. In the analysis of unigene expression profiles, 327 unigenes were found to be upregulated and 153 unigenes were found to be downregulated in the BPA exposure group compared to the control group. Dopaminergic signaling pathway-related genes were significantly downregulated in the BPA exposure group. Furthermore, we found that serum dopamine concentrations decreased and TUNEL (terminal deoxynucleotidyl transferase 2-deoxyuridine, 5-triphosphate nick end labeling) staining was present in dopamine neurons enriched regions in the brain after BPA exposure, suggesting that BPA may disrupt dopaminergic processes. A KEGG analysis revealed that genes involved in the fluid shear stress and atherosclerosis pathway were highly significantly enriched. In addition, the qRT-PCR results for fluid shear stress and atherosclerosis pathway-related genes and the vascular histology of the brain showed that BPA exposure could damage blood vessels and induce brain atherosclerosis. The results of this work provide insights into the biological effects of BPA on dopamine synthesis and blood vessels in goldfish brain and could lay a foundation for future BPA neurotoxicity studies.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1886-1886
Author(s):  
Keri B Vartanian ◽  
Brad J Blakley ◽  
Owen JT McCarty ◽  
Stephen Hanson ◽  
Monica T Hinds

Abstract Atherosclerotic vascular disease and dysfunction of endothelial cells (ECs), which form the continuous lining of blood vessels, preferentially develop in regions where blood vessels are bifurcated and curved. In these regions, ECs are exposed to low, oscillatory fluid shear stress (FSS), are cobblestone in morphology, and have an athero-prone phenotype. In contrast, in regions where FSS is high and unidirectional, ECs are elongated parallel to the direction of flow and have an athero-protective phenotype. Although previous research has correlated FSS with EC morphology and phenotype, the effects of dramatic changes in cell morphology alone, i.e., in the absence of FSS differences, on EC functions remain largely unknown. To determine the role of EC shape on cell function, we investigated the regulation of EC hemostatic functions, an important measure of EC dysfunction and atherosclerosis, by elongated and cobblestone ECs (with shape independent of FSS). To separate EC shape from FSS-induced effects, surface engineering was used to create elongated ECs on micropatterned collagen I lanes (25 μm wide with 100 μm spacing). By 24 hrs, ECs elongated on these micropatterned lanes had a comparable shape index and cytoskeletal alignment as ECs elongated by exposure to 24 hrs of 12.5 dyn/cm2 FSS. qtPCR was used to determine the gene expression of the following markers of coagulant/hemostatic functions: tissue factor (TF), tissue factor pathway inhibitor (TFPI), endothelial nitric oxide synthase (eNOS), thrombomodulin (TM), and von Willebrand Factor (vWF). PCR results indicated that EC elongation alone upregulated expression of TF (1.41 ± 0.28) and decreased expression of eNOS (0.78 ± 0.07). vWF was downregulated (0.59 ± 0.11). Micropattern elongated ECs expressed TFPI and TM at levels comparable to cobblestoneappearing ECs (1.04 ± 0.08 and 1.12 ± 0.04, respectively). To determine whether these changes in gene expression had functional consequences, the generation of thrombin (factor X activation, FXa) and platelet adhesion were studied. Micropattern elongated ECs were able to convert more FX to FXa per cell compared to cobblestone ECs (0.88 ± 0.20 and 0.065 ± 0.01 pg/cell, respectively), indicating an increase in TF activity. This data is consistent with the increased TF gene expression seen in micropattern elongated ECs. Platelet adhesion studies also suggested a thrombogenic phenotype for micropattern elongated ECs, with more platelets adhering and spreading per cell on elongated (8.82 ± 1.47) versus cobblestone (4.64 ± 1.49) ECs. Overall, these findings suggest that EC shape is an independent variable that can regulate cell hemostatic functions, such as thrombotic potential. Surprisingly, elongated ECs exhibited a more thrombogenic phenotype, findings that contrast results obtained with FSS-elongated ECs, both in vitro and in vivo. Thus, both cell shape and FSS may play important and in some instances opposing roles in regulating EC hemostatic functions in the maintenance of vascular integrity.


2003 ◽  
Vol 285 (3) ◽  
pp. H1072-H1080 ◽  
Author(s):  
Shu Q. Liu ◽  
Dalin Tang ◽  
Christopher Tieche ◽  
Paul K. Alkema

Smooth muscle cells (SMCs) are organized in various patterns in blood vessels. Whereas straight blood vessels mainly contain circumferentially aligned SMCs, curved blood vessels are composed of axially aligned SMCs in regions with vortex blood flow. The vortex flow-dependent feature of SMC alignment suggests a role for nonuniform fluid shear stress in regulating the pattern formation of SMCs. Here, we demonstrate that, in experimental models with vascular polymer implants designed for the observation of neointima formation and SMC migration under defined fluid shear stress, nonuniform shear stress possibly plays a role in regulating the direction of SMC migration and alignment in the neointima of the vascular implant. It was found that fluid shear stress inhibited cell growth, and the presence of nonuniform shear stress influenced the distribution of total cell density and induced the formation of cell density gradients, which in turn directed SMC migration and alignment. In contrast, uniform fluid shear stress in a control model influenced neither the distribution of total cell density nor the direction of SMC migration and alignment. In both the uniform and nonuniform shear models, the gradient of total cell density was consistent with the alignment of SMCs. These observations suggest that nonuniform shear stress may regulate the pattern formation of SMCs, possibly via mediating the gradient of cell density in the neointima of vascular polymer implants.


2015 ◽  
Vol 137 (2) ◽  
Author(s):  
Julia C. Chen ◽  
Mardonn Chua ◽  
Raymond B. Bellon ◽  
Christopher R. Jacobs

Osteogenic lineage commitment is often evaluated by analyzing gene expression. However, many genes are transiently expressed during differentiation. The availability of genes for expression is influenced by epigenetic state, which affects the heterochromatin structure. DNA methylation, a form of epigenetic regulation, is stable and heritable. Therefore, analyzing methylation status may be less temporally dependent and more informative for evaluating lineage commitment. Here we analyzed the effect of mechanical stimulation on osteogenic differentiation by applying fluid shear stress for 24 hr to osteocytes and then applying the osteocyte-conditioned medium (CM) to progenitor cells. We analyzed gene expression and changes in DNA methylation after 24 hr of exposure to the CM using quantitative real-time polymerase chain reaction and bisulfite sequencing. With fluid shear stress stimulation, methylation decreased for both adipogenic and osteogenic markers, which typically increases availability of genes for expression. After only 24 hr of exposure to CM, we also observed increases in expression of later osteogenic markers that are typically observed to increase after seven days or more with biochemical induction. However, we observed a decrease or no change in early osteogenic markers and decreases in adipogenic gene expression. Treatment of a demethylating agent produced an increase in all genes. The results indicate that fluid shear stress stimulation rapidly promotes the availability of genes for expression, but also specifically increases gene expression of later osteogenic markers.


2006 ◽  
Vol 45 (3) ◽  
pp. e51
Author(s):  
Caroline Cheng ◽  
Dennie Tempel ◽  
Luc van Damme ◽  
Rien van Haperen ◽  
Rob Krams ◽  
...  

2019 ◽  
Vol 234 (9) ◽  
pp. 16312-16319 ◽  
Author(s):  
Danyang Yue ◽  
Mengxue Zhang ◽  
Juan Lu ◽  
Jin Zhou ◽  
Yuying Bai ◽  
...  

2017 ◽  
Vol 16 (6) ◽  
pp. 8699-8708 ◽  
Author(s):  
Liyin Yu ◽  
Xingfeng Ma ◽  
Junqin Sun ◽  
Jie Tong ◽  
Liang Shi ◽  
...  

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