Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell proliferation: A comparative proteomic analysis

Background

Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study.

Methods

We utilized proteomic study to indentify the protein expression changes of Sertoli TM4 cells treated with 10^− 8 M and 10^− 5 M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis.

Results

Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10^− 8 M and 10^− 5 M BPA, respectively, for 24 h. Exposure to 10^− 5 M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10^− 8 M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages.

Conclusions

Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism.

General significance

Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.     

Association analysis of ERBB2 amplicon genetic polymorphisms and STARD3 expression with risk of gastric cancer in the Chinese population

The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing steroidogenic acute regulatory-related lipid transfer domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, haplotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P = 0.043, odds ratio [OR] = 0.805, 95% confidence intervals [95% CI] = 0.643–0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P = 0.021, OR = 2.882, 95% CI = 1.173–7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). The expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P = 0.004), alcohol drinking (P < 0.001), tumor location (P = 0.007), histological type (P = 0.005) and differentiation (P = 0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population.     

Occurrence and development of Eucryptorrhynchus brandti and E. chinensis (Coleoptera: Curculionidae) on Ailanthus altissima trees subjected to different levels of mechanical damage

Eucryptorrhynchus brandti (Harold) and E. chinensis (Oliver) are herbivores of Ailanthus altissima (Mill.) Swingle (tree of heaven) in China. Eucryptorrhynchus brandti has been recommended as a potential biological control agent of A. altissima in North America. In China, the majority of adults of both species were found on tree trunks 0–5 m above the ground, from May to September. In October and November, most adults were found at the base of A. altissima trees. Trees were subjected to different levels of mechanical injury: very low mechanical injury, one to two 0.015 m² bark sections were removed; low, two to four bark sections were removed; moderate, 8 to 22 bark sections removed; high, tree was girdled; and extreme, tree was felled and the remaining stump was sampled. Very low and low mechanical injury trees had very few adult emergence holes with few larvae developing beyond the first or second instar after 29 months. The health of these trees remained good. An increase in adult emergence holes occurred in moderately injured trees that appeared as healthy as very low to low mechanically injured trees. This may indicate that only a small increase in tree stress can increase the adult emergence rate and thus hasten a decline in tree health. Moderate, high and extreme mechanically injured trees had significantly more emergence holes/m than very low and low injured trees and late larval stages were present. The development of Eucryptorrhynchus species was more successful the greater the degree of mechanical injury. Based on this study both Eucryptorrhynchus species appear to be secondary pests of A. altissima in China.     

家族性高胆固醇血症患者低密度脂蛋白受体基因复合杂合突变分析

目的:对1例临床确诊为纯合型家族性高胆固醇血症(FH)先证者及其核心家系成员进行基因检测分析,探讨患儿发病的分子病理基础.方法:收集先证者及父母血标本及临床资料,酚氯仿法提取基因组DNA,DNA直接测序方法检测低密度脂蛋白受体(LDL-R)基因18个外显子和启动子及载脂蛋白B(ApoB100)R3500Q位点,核苷酸序列分析结果与Gen Bank比对寻找突变.结果:(1)先证者三尖瓣轻度关闭不全,先证者父母双侧颈总动脉内-中膜增厚,先证者母亲左侧颈内动脉起始处后壁多发混合回声斑块(2)该家系排除ApoB100基因R3500Q突变;(3)先证者LDL-R基因第13外显子发生A606T和D601Y复合杂合突变,前者第1879位G→A碱基置换,导致丙氨酸改变为苏氨酸,后者为1864位G>T碱基置换,导致天冬氨酸改变为酪氨酸,其父为携带A606T突变的杂合子,其母为携带D601Y突变的杂合子.结论:先证者LDL-R基因存在A606T和D601Y复合杂合突变,它们分别来源于父系及母系遗传.     

Characterization of the interaction between 2′-deoxyuridine and human serum albumin

The binding of 2′-deoxyuridine to human serum albumin (HSA) was investigated by fluorescence spectroscopy in combination with molecular modeling under simulation of physiological conditions. The quenching mechanism was suggested to be static according to the fluorescence measurement. The thermodynamic parameters: enthalpy change (ΔH) and entropy change (ΔS) were calculated to be −18.87 kJ/mol and 24.00 J/(mol K) according to the Vant’Hoff equation. These data suggest that hydrophobic interactions are the predominant intermolecular forces stabilizing the complex. Experimental results are in agreement with the results obtained by molecular modeling study. In addition, the effects of common ions on the binding constants were also studied at room temperature.     

Structural elucidation and immuno-stimulating activity of an acidic heteropolysaccharide (TAPA1) from Tremella aurantialba

A novel acidic heteropolysaccharide (TAPA1) was purified from hot water extracts of Tremella aurantialba fruiting bodies by DEAE-Sepharose Fast Flow and Sephacryl S-500 High-Resolution Chromatography. The heteropolysaccharide had a molecular weight of ca. 1.35 × 10⁶ Da, and a carbohydrate content estimated to be ∼98.7% by the phenol-sulfuric acid method. It was composed mainly of d-mannose, d-xylose, and d-glucuronic acid in the ratio of ca. 5:4:1, along with trace amounts of d-galacturonic acid and d-glucose. Monosaccharide compositional analysis and GC-MS of methylated derivatives, combined with ¹H and ¹³C NMR spectroscopies (including COSY, TOCSY, NOESY, HSQC, and HMBC spectra), revealed TAPA1 to consist of an α-(1→3)-linked mannopyranosyl backbone, partially substituted at position 4 with xylose side chains, and at position 2 with side chains composed of either xylose, mannose, and glucuronic acid or of xylose and mannose. Bioactivity testing showed that TAPA1 stimulated the proliferation of mouse spleen lymphocytes in vitro.     

Proteolytic regulatory mechanism of chemerin bioactivity

Chemerin is a novel chemoattractant recognized by chemokine-like receptor 1 （CMKLR1）, a serpentine receptor expressed primarily by plasmacytoid dendritic cells, natural killer cells, and macrophages. Human pro- chemerin circulates in plasma as an inactive precursor. Its chemotactic activity is expressed upon cleavage of the C-terminal amino acid residues by proteases of the coagulation, fibrinolytic, and inflammatory system. The C-terminal cleavage site of prochemerin is highly conservative, indicating that the proteolytic regulation of chemerin bioactivity is a common mechanism undertaken by different species. In this review, we summarized chemerin-proteases interactions（ chemerin receptors, and their importance in normal and pathologic conditions.     

六盘山叠叠沟小流域典型坡面土壤水分的植被承载力

确定土壤水分的植被承载力是我国北方半干旱地区合理调控土壤水分和植被生长关系、科学恢复林草植被的核心问题。我国北方半干旱地区的土壤水分主要来自大气降水, 作为土壤水分限制型生态系统的坡面植被, 植物种类和植被密度等结构特征与降水量紧密相关。根据六盘山石质山区的特点, 基于水量平衡原理, 建立了阴坡华北落叶松(Larix principis-rupprechti)和阳坡草地的土壤水分植被承载力数学模型, 即由4~10月的生长季降雨量(P)计算得到可承载的叶面积指数(Leaf area index, LAI)公式: LAI_tree= exp((0.773 1×P-186.12)/146.46)和LAI_grass= exp((0.511 2×P-345.93)/227.89), 并提出了考虑坡面水分再分配影响的不同坡位的土壤水分植被承载力计算方法。阴坡华北落叶松的植被承载力(用LAI表示)从坡顶的1.45升高到坡中的4.83, 然后稳定在3.0~3.3。对于阳坡草地, 土壤水分可承载的LAI从坡顶的0.37上升到坡中的0.46, 然后在0.41~0.47之间变动, LAI的计算值与实测值较为接近, 计算结果比较合理。     

C群奈瑟氏脑膜炎球菌荚膜多糖-TT结合疫苗的制备及其在小鼠体内免疫原性的研究

将C群脑膜炎球菌荚膜多糖以ADH作为间隔剂与TT结合形成GCMP-TT结合疫苗,然后用此结合疫苗免疫NIH小鼠,结果显示使用GCMP免疫小鼠后仅能产生较低水平抗GCMP的IgG抗体,而用GCMP-TT免疫后小鼠血清中产生了较GCMP免疫显著增高抗GCMP的IgG抗体,并且GCMP-TT组第二次和第三次免疫后与初次免疫相比,IgG抗体水平均有显著升高(P<0.01),表明GCMP-TT结合疫苗具有免疫记忆和再次免疫加强应答效应。补体介导的血清抗体体外杀菌试验结果证明,GCMP-TT结合疫苗组免疫小鼠诱导的抗体IgG比GCMP组具有增强的体外杀菌活性。     

Correlation of volatile profiles of twenty mango cultivars with their susceptibilities to mango gall fly infestation

Mango gall fly (Procontarinia matteiana) is an orchard pest that parasitises flush leaves of mango and serious outbreaks may result in reduced fruit yield. The trigger for infestation is unknown, but terpenes emitted by the leaves appear to play a role in attraction. Metabolic profiles of three mango cultivars of varying susceptibility to mango gall fly attack were obtained by headspace profiling using GC-FID and GC-MS analysis. Chemometric models constructed from the data revealed that three terpenes, α- and β-pinene and camphene could be useful as biomarkers for susceptibility. Headspace profiles of twenty other cultivars, naturally exposed to gall fly, were obtained in the same way. Susceptibility or resistance of these cultivars was predicted using the developed orthogonal partial least squares model. Predictive outcomes were thereafter verified by visual examination of the leaves to detect gall formation, an indication of gall fly infestation. The model was found to predict the susceptibility or resistance of 90% of the cultivars accurately. This finding indicates the contributory role of the three terpene biomarkers in mango gall fly interaction and may direct future studies to determine their inter-relationship.