Induction of intracellular calcium concentration by environmental benzo(a)pyrene involves a β2-adrenergic receptor/adenylyl cyclase/Epac-1/inositol 1,4,5-trisphosphate pathway in endothelial cells

Polycyclic aromatic hydrocarbons (PAHs) such as benzo(a)pyrene (B(a)P) are widely distributed environmental contaminants, known as potent ligands of the aryl hydrocarbon receptor (AhR). These chemicals trigger an early and transient increase of intracellular calcium concentration ([Ca(2+)](i)), required for AhR-related effects of PAHs. The mechanisms involved in this calcium mobilization were investigated in the present study. We demonstrated that B(a)P-mediated [Ca(2+)](i) induction was prevented in endothelial HMEC-1 cells by counteracting β2-adrenoreceptor (β2ADR) activity using pharmacological antagonists, anti-β2ADR antibodies, or siRNA-mediated knockdown of β2ADR expression; by contrast, it was strongly potentiated by β2ADR overexpression in human kidney HEK293 cells. B(a)P was shown, moreover, to directly bind to β2ADR, as assessed by in vitro binding assays and molecular modeling. Pharmacological inhibition and/or siRNA-mediated silencing of various signaling actors acting downstream of β2ADR in a sequential manner, such as G protein, adenylyl cyclase, Epac-1 protein, and inositol 1,4,5-trisphosphate (IP(3))/IP(3) receptor, were next demonstrated to prevent B(a)P-induced calcium signal. Inhibition or knockdown of these signaling elements, as well as the use of chemical β-blockers, were finally shown to counteract B(a)P-mediated induction of cytochrome P-450 1B1, a prototypical AhR target gene. Taken together, our results show that B(a)P binds directly to β2ADR and consequently utilizes β2ADR machinery to mobilize [Ca(2+)](i), through activation of a G protein/adenylyl cyclase/cAMP/Epac-1/IP(3) pathway. This β2ADR-dependent signaling pathway activated by PAHs may likely be crucial for PAH-mediated up-regulation of AhR target genes, thus suggesting a contribution of β2ADR to the health-threatening effects of these environmental pollutants.     

Emission Estimates of Particulate PAHs from Biomass Fuels Used in Delhi,India

The emission factors for particulate-phase polycyclic aromatic hydrocarbons (PAHs) were evaluated for various biomass fuels (fuelwood, dung cakes, and agricultural residue) that are being commonly used in Delhi as a source of energy. Emission factors of total particulate PAHs varied from 35.9 ± 1.9 to 59.7 ± 4.4 mg/kg. Higher levels of total PAHs and particulate matter (PM) were found from dung cakes as compared to fuelwood and agricultural residue. The emission factors for PM from dung cake, fuelwood, and agricultural residue are 25 ± 8, 15 ± 3.2, and 12.1 ± 9.4 g/kg, respectively. The total PAH emissions showed an increase with high particulate matter emission rates and lower combustion efficiency. Fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene constituted the major fraction of PAH emissions from all biomass fuels. The annual budget estimates (total emissions per year) for PAHs and PM from biomass fuels used in Delhi are 30.5 ± 2.3 Mg (Megagrams) and 11.6 ± 4.4 Gg (Gigagrams), respectively. An attempt has also been made to evaluate the preliminary budget estimates of PAHs and PM emitted from the use of biomass fuels as a source of energy in India by using the emission factors obtained in the present study.     

链霉菌来源的苯并异色烷醌家族抗生素的生物合成

苯并异色烷醌(benzoisochromanequinones,BIQs)家族抗生素是由链霉菌产生的聚酮类抗生素,其芳香聚酮母核结构中含有并联的两个芳香环和一个吡喃环,具有抗菌、抗肿瘤等多种生物学活性。BIQ抗生素聚酮链的早期生物合成过程代表了芳香聚酮抗生素母核的典型合成机制,而不同的后期修饰则决定了它们结构和生物学活性的多样性。在过去的二十几年中,以放线紫红素和美达霉素为研究重点,BIQ家族抗生素的生物合成机制逐渐得到揭示,但在后期结构修饰方面仍有许多问题有待解决。本文对BIQ家族抗生素的生物合成机制研究进行了综述,比较了不同BIQ家族抗生素结构特点、生物学活性,并重点阐述了它们生物合成中的后期结构修饰和调控过程的研究进展,并对BIQ抗生素在代谢工程方面的研究进行了展望。     

Review on proteomic analyses of benzo[a]pyrene toxicity

Benzo[a]pyrene (BaP), a five-ring polycyclic aromatic hydrocarbon, is a well-recognized environmental pollutant. Coal-processing waste products, petroleum sludge, asphalt, creosote, and tobacco smoke, all contain high levels of BaP. Exposure to BaP elicits many adverse biological effects, including tumor formation, immunosuppression, teratogenicity, and hormonal effects. In addition to the genetic damage caused by BaP exposure, several studies have indicated the disruption of protein-protein signaling pathways. However, contrary to the large number of studies on BaP-induced DNA damage, only few data have been gathered on its effects at the protein level. This review highlights all proteomic studies to date used for assessing the toxicity of BaP and its metabolites in various organ systems. It will also give an overview on the role proteomics may play to elucidate the mechanisms underlying BaP toxicity.     

Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study

BACKGROUND: There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case‐control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. METHODS: Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self‐reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. RESULTS: The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58–1.67), septal defects (AOR, 1.28; 95% CI, 0.86–1.90), or with any isolated CHD subtype. CONCLUSIONS: Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population‐based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.     

Bioelectrochemical stimulation of petroleum hydrocarbon degradation in saline soil using U-tube microbial fuel cells

Bioremediation is a cost-effective and eco-friendly approach to decontaminate soils polluted by petroleum hydrocarbons. However, this technique usually requires a long time due to the slow degradation rate by bacteria. By applying U-tube microbial fuel cells (MFCs) designed here, the degradation rate of petroleum hydrocarbons close to the anode (<1 cm) was enhanced by 120% from 6.9 ± 2.5% to 15.2 ± 0.6% with simultaneous 125 ± 7 C of charge output (0.85 ± 0.05 mW/m(2) , 1 kΩ) in the tested period (25 days). Hydrocarbon fingerprint analysis showed that the degradation rate of both alkanes and polycyclic aromatic hydrocarbons (PAHs) was accelerated. The decrease of initial water content from 33% to 28% and 23% resulted in a decrease on charge output and hydrocarbon degradation rate, which could be attributed to the increase of internal resistance. A salt accumulation was observed in each reactor due to the evaporation of water from the air-cathode, possibly inhibited the activity of exoelectrogenic bacteria (EB) and resulted in the elimination of the current at the end of the tested period. The number of hydrocarbon degradation bacteria (HDB) in soil close to the anode increased by nearly two orders of magnitude in the MFC assisted system (373 ± 56 × 10(3) CFU/g-soil) than that in the disconnected control (8 ± 2 × 10(3) CFU/g-soil), providing a solid evidence for in situ biostimulation of HDB growth by colonization of EB in the same system.     

Aryl–aryl interactions in designed peptide folds: Spectroscopic characteristics and optimal placement for structure stabilization

We have extended our studies of Trp/Trp to other Aryl/Aryl through‐space interactions that stabilize hairpins and other small polypeptide folds. Herein we detail the NMR and CD spectroscopic features of these types of interactions. NMR data remains the best diagnostic for characterizing the common T‐shape orientation. Designated as an edge‐to‐face (EtF or FtE) interaction, large ring current shifts are produced at the edge aryl ring hydrogens and, in most cases, large exciton couplets appear in the far UV circular dichroic (CD) spectrum. The preference for the face aryl in FtE clusters is W ? Y ≥ F (there are some exceptions in the Y/F order); this sequence corresponds to the order of fold stability enhancement and always predicts the amplitude of the lower energy feature of the exciton couplet in the CD spectrum. The CD spectra for FtE W/W, W/Y, Y/W, and Y/Y pairs all include an intense feature at 225–232 nm. An additional couplet feature seen for W/Y, W/F, Y/Y, and F/Y clusters, is a negative feature at 197–200 nm. Tyr/Tyr (as well as F/Y and F/F) interactions produce much smaller exciton couplet amplitudes. The Trp‐cage fold was employed to search for the CD effects of other Trp/Trp and Trp/Tyr cluster geometries: several were identified. In this account, we provide additional examples of the application of cross‐strand aryl/aryl clusters for the design of stable β‐sheet models and a scale of fold stability increments associated with all possible FtE Ar/Ar clusters in several structural contexts. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 337–356, 2016.