Bisphenol A (BPA) is widely used in plastic products, through which humans are exposed to it. Accumulating evidence suggests that BPA exposure is associated with b-cell dysfunction. Mitochondrial defects can cause impairment and failure of b cells, but there is little information about the effects of BPA on the mitochondrial function of b cells. In this study, we assessed the role of mitochondria-mediated mechanisms underlying BPA-induced b-cell dysfunction and resulting b-cell apoptosis. INS-1 cells were cultured with 0, 0.0020, 0.020, 0.20, or 2.0 lM BPA. Cell viability, glucose-stimulated insulin secretion (GSIS), and mitochondrial function were examined. The mitochondrial apoptotic pathway was also analyzed at molecular level. We found that BPA suppressed cell viability and disturbed GSIS in a dose-dependent manner. Positive Annexin-propidium iodide (PI) staining and altered expression of Bcl-2 family members and caspases in INS-1 cells indicated that the cells progressively became apoptotic after BPA exposure. Additionally, BPA-induced apoptosis was associated with mitochondrial defects in b cells, as evidenced by depletion of ATP, release of cytochrome c, loss of mitochondrial mass and membrane potential, and alterations in expression of genes involved in mitochondrial function and metabolism. Taken together, these findings provide strong evidence that BPA triggers INS-1 cells dysfunction and apoptosis may be meditated via the mitochondrial pathway.

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Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits.

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The 2 structurally and functionally related peptides, neuropeptide B (NPB) and neuropeptide W (NPW), together with their receptor(s) (NPBWR1/NPBWR2) constitute the NPB/NPW system, which acts mainly on the central nervous system to regulate many physiological processes in mammals. However, little is known about this NPB/NPW system in nonmammalian vertebrates. In this study, the functionality and expression of this NPB/NPW system and its actions on the pituitary were investigated in chickens. The results showed that: 1) chicken NPB/NPW system comprises an NPB peptide of 28 amino acids (cNPB28), an NPW peptide of 23 or 30 amino acids (cNPW23/cNPW30), and their 2 receptors (cNPBWR1 and cNPBWR2), which are highly homologous to their human counterparts. 2) Using a pGL3-CRE-luciferase reporter system, we demonstrated that cNPBWR2 expressed in Chinese hamster ovary cells can be potently activated by cNPW23 (not cNPB28), and its activation inhibits the intracellular cAMP signaling pathway, whereas cNPBWR1 shows no response to peptide treatment, suggesting a crucial role of cNPBWR2 in mediating cNPW/cNPB actions. 3) Quantitative real-time PCR revealed that cNPW and cNPB are widely expressed in chicken tissues, including hypothalamus, whereas cNPBWR1 and cNPBWR2 are mainly expressed in brain or pituitary. 4) In accordance with abundant cNPBWR2 expression in pituitary, cNPW23 could dose dependently inhibit GH and prolactin secretion induced by GHRH and vasoactive intestinal polypeptide, respectively, in cultured chick pituitary cells, as monitored by Western blotting. Collectively, our data reveal a functional NPB/NPW system in birds and offer the first proof that NPW can act directly on pituitary to inhibit GH/prolactin secretion in vertebrates.

To study the spatial distributions and seasonal differences of concentrations, source identification, and phase partitioning of polycyclic aromatic hydrocarbons (PAHs) in surface water, intensive sampling was carried out along the marginal seas of China in four seasons. In the northern South China Sea (SCS), the highest PAH levels occurred in the summer (July to August) and autumn (October to November). In the East China Sea (ECS) and the Yellow Sea, the highest occurred in the summer (August) and winter (December). In all areas, the lowest PAH levels were found in the spring (May to June). The estimated mass inventory of PAHs in the surface water (0-5 m) of the northern SCS and ECS accounted for less than 8% of PAHs outflow into the offshore environment. That showed the consistent seasonal variation with PAHs levels. Land- and ocean-based emissions, surface runoff, and the open seawater dilution were the most important environmental factors influencing the seasonal heterogeneity and the spatial distributions of PAH in the surface water. The decline of observed organic carbon normalized partition coefficients in the four seasons was probably affected by the presence of submicrometer-sized soot particles accompanying the PAH outflow from China.