| 1. |
- Asplund, Annika, 1979, et al.
(författare)
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Hypoxic regulation of secreted proteoglycans in macrophages.
- 2010
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 20:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Macrophages are prominent in hypoxic areas of atherosclerotic lesions, and their secreted proteoglycans (PG), such as versican, can modulate the retention of lipoproteins and the activity of enzymes, cytokines, and growth factors involved in atherogenesis. In this study, we report the effects of hypoxia on PG secreted by human monocyte-derived macrophages (HMDM) and the potential regulation by the transcription factor hypoxia-inducible factor (HIF-1alpha and HIF-2alpha). We found that versican co-localized with HIF-1alpha in macrophage-rich areas in human advanced atherosclerotic lesions. Versican and perlecan mRNA expression increased after exposure to 0.5% O(2) (hypoxia) compared with 21% O(2) (control cells). Using precursors to GAG biosynthesis combined with immunoabsorption with a versican antibody an increased versican synthesis was detected at hypoxia. Furthermore, siRNA knockdown of HIF-1alpha and HIF-2alpha in THP-1 cells showed that the hypoxic induction of versican and perlecan mRNA expression involved HIF signaling. Versican expression was co-regulated by HIF-1alpha and HIF-2alpha but expression of perlecan was influenced only by HIF-1alpha and not by HIF-2alpha knockdown. The results show that oxygen concentration is an important modulator of PG expression in macrophages. This may be a novel component of the complex role of macrophages in atherosclerosis.
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| 2. |
- Dahlberg, Anna-Karin, et al.
(författare)
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Recovery discrepancies of OH-PBDEs and polybromophenols in human plasma and cat serum versus herring and long-tailed duck plasma
- 2014
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 94, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as metabolites of polybrominated diphenyl ethers (PBDEs) and/or as natural products. The OH-PBDEs and polybromophenols have come into focus over the last decade due to their abundance in biota and their potential adverse health effects. The present recovery study aims to validate a commonly used method (published by Hovander et al. 2000) for OH-PBDE analysis in human plasma. Further, the authors intended to determine the method's applicability to serum/plasma matrices from other species than humans. The investigated matrices were human plasma, cat serum, herring- and long-tailed duck plasma. The recovery study included nine OH-PBDEs, four polybromophenols and three methoxylated PBDEs (MeO-PBDEs). Five replicates of each matrix were spiked with these compounds at two dose levels; a low dose (0.5 ng) and a high dose (5 ng) and were cleaned up according to the Hovander method. The recovery of OH-PBDEs and polybromophenols in human plasma and cat serum were high and reproducible at both dose levels whereas the recovery for herring and long-tailed duck plasma were low and insufficient with great variability amongst OH-PBDE congeners at both dose levels. Our data show that the method can be fully applied to matrices like human plasma and cat serum but not for herring and long-tailed duck plasma without further method development. Hence care needs to be taken when applying the method onto other blood matrices without validation since the present study have demonstrated that the recoveries may differ amongst OH-PBDE congeners and specie.
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| 3. |
- Enhus, Carolina, et al.
(författare)
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Natural production of brominated aromatic compounds in the red alga Ceramium tenuicorne
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SummaryHigh levels of the toxic, brominated substances; hydroxylated polybrominated diphenyl ethers (OH-PBDEs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs), and 2,4,6-tribromophenol (2,4,6-TBP) have been found in Baltic biota with levels fluctuating over seasons. A growing body of evidence is pointing towards filamentous algae as a natural producer of these chemicals. However, conclusive scientific evidence supporting this hypothesis is lacking and why such production occurs has not comprehensively been addressed. This pilot study, carried out with a limited set of replicates reveals a production of 6-OH-BDE47, 6-OH-BDE137, and 2,4,6-TBP in the filamentous alga,Ceramium tenuicorne, a common red alga both in the Baltic Sea and in temperate waters. When exposed to grazing or strong light, monocultures of the female marine clone of C. tenuicorne tended to produce elevated levels of 2,4,6-TBP compared to undamaged controls. When exposed to increased levels of salinity, monocultures of the female brackish clone of C. tenuicorne tended to produce elevated levels of 2,4,6-TBP compared to undamaged controls. Algae collected from the Swedish east coast also tended to produce higher levels of 2,4,6-TBP than algae collected from the west coast. From field collected material, a seasonal variation with a peak of OH-PBDEs, MeO-PBDE, and TBP concentrations in July- August could also be detected.The results of this study open up for further studies regarding natural production of brominated aromatic compounds by filamentous algae as a response to environmental stress. Increased understanding regarding sources and possible variations in production of brominated aromatic compounds is crucial for successful monitoring and assessment of environmental status.
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| 4. |
- Haglund, Peter S., et al.
(författare)
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Powerful GC-TOF-MS Techniques for Screening, Identification and Quantification of Halogenated Natural Products
- 2013
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Ingår i: Mass Spectrometry. - 2186-5116. ; 2:Special Issue, s. S0018-
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Tidskriftsartikel (refereegranskat)abstract
- Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC TOFMS) and gaschromatography/high-resolution time-of-flight mass spectrometry (GC-HRT) were used to detect and identify halogenatednatural products (HNPs) in tissue homogenate, in this case brominated analytes present in a marine snail. Two classes of brominatedanthropogenic compounds, polybrominated diphenyl ethers (PBDEs) and brominated dibenzofurans, were analyzedfor comparison. Following conventional preparation, the sample was analyzed using GC×GC-TOF-MS. Isotope ratio scriptswere used to compile a list of putatively brominated analytes from amongst the thousands of features resolved in the twodimensionalchromatogram. The structured nature of the chromatogram was exploited to propose identifications for severalclasses of brominated compounds, and include additional candidates that fell marginally outside the script tolerances. Thesample was subsequently analyzed by GC-HRT. The high-resolution mass spectral data confirmed many formula assignments,facilitated confident assignment of an alternate formula when an original proposal did not hold, and enabled unknown identification.Identified HNPs include hydroxylated and methoxylated PBDE analogs, polybrominated dibenzo-p-dioxins (PBDDs)and hydroxyl-PBDDs, permitting the environmental occurrence and fate of such compounds to be studied.
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| 5. |
- Haglund, Peter, et al.
(författare)
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Temporal Variations of Polybrominated Dibenzo-p-Dioxin and Methoxylated Diphenyl Ether Concentrations in Fish Revealing Large Differences in Exposure and Metabolic Stability
- 2010
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:7, s. 2466-73
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Tidskriftsartikel (refereegranskat)abstract
- The concentrations of polybrominated dibenzo-p-dioxins (PBDDs) and polybrominated methoxylated diphenyl ethers (MeO-PBDEs) were investigated in perch (Perca fluviatilis) collected from a Baltic Sea background contaminated area between 1990 and 2005. No temporal trend was found, but large variations were observed - up to 5-fold and 160-fold differences in MeO-PBDE and PBDD concentrations, respectively - between consecutive years, suggesting that retention of these compounds, particularly the PBDDs, is limited. Examination of the congener profiles using principal component analysis (PCA) and correlation analysis indicated that MeO-PBDEs without adjacent substituents (6-MeO-BDE47) or with two adjacent substituents (2'-MeO-BDE68 and 6-MeO-BDE90) are retained more than MeO-PBDEs with three adjacent substituents (6-MeO-BDE85 and 6-MeO-BDE99) and that 1,3,6,8-tetraBDD and 1,3,7,9-tetraBDD are retained more than the other PBDDs which have vicinal hydrogen. Debromination could explain the limited retention of 6-MeO-PBDE85 and 6-MeO-BDE99 and the absence of 2-MeO-BDE123 and 6-MeO-BDE137, and cytochrome P-450 mediated oxidation could explain the limited retention of PBDDs containing vicinal hydrogen. The levels of organobromines, especially MeO-PBDEs, were found to covary with water conditions related to primary production, for example temperature, depth visibility, and inorganic nutrient concentrations, which also favor fish productivity. The results suggest natural production of MeO-PBDEs and PBDDs and imply that they fluctuate considerably over time, as do common marine toxins in fish. Thus, assessments of human and environmental risk should consider both the average and peak concentrations of these contaminants in marine biota.
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| 6. |
- John, Sternbeck, et al.
(författare)
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Organiska miljögifter i fisk från svenska bakgrundsområden
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Fisk från nio svenska lokaler, representerande sötvatten, kust och utsjö, har analyserats på PBDE (polybromerade difenyletrar), HBCD, PAH (polycykliska aromatiska kolväten), Klorerade bensener, PCB, ftalater, och klorerade dioxiner och furander i fiskmuskel. Dessutom har pentaklorfenol, triclosan och tetrabrombisfenol A analyserats i fiskgalla från tre av dessa lokaler.
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| 7. |
- Legradi, Jessica, et al.
(författare)
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Disruption of oxidative phosphorylation (OXPHOS) by hydroxylated polybrominated diphenyl ethers (OH-PBDEs) present in the marine environment
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:24, s. 14703-14711
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are of growing concern, as they have been detected in both humans and wildlife and have been shown to be toxic. Recent studies have indicated that OH-PBDEs can be more toxic than PBDEs, partly due to their ability to disrupt oxidative phosphorylation (OXPHOS), an essential process in energy metabolism. In this study, we determined the OXPHOS disruption potential of 18 OH-PBDE congeners reported in marine wildlife using two in vitro bioassays, namely the classic rat mitochondrial respiration assay, and a mitochrondrial membrane potential assay using zebrafish PAC2 cells. Single OH-PBDE congeners as well as mixtures were tested to study potential additive or synergistic effects. An environmental mixture composed of seven OH-PBDE congeners mimicking the concentrations reported in Baltic blue mussels were also studied. We report that all OH-PBDEs tested were able to disrupt OXPHOS via either protonophoric uncoupling and/or inhibition of the electron transport chain. Additionally we show that OH-PBDEs tested in combinations as found in the environment have the potential to disrupt OXPHOS. Importantly, mixtures of OH-PBDEs may show very strong synergistic effects, stressing the importance of further research on the in vivo impacts of these compounds in the environment
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| 8. |
- Lindqvist, Dennis, et al.
(författare)
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Lipid-soluble conjugates of hydroxylated polybrominated diphenyl ethers in blue mussels from the Baltic Sea
- 2014
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 21:2, s. 954-961
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) of proposed natural origin have been detected throughout the food web of the Baltic Sea. Some OH-PBDEs have been shown to disrupt oxidative phosphorylation and the thyroid hormone system in exposed organisms. This paper describes an investigation into the fate of OH-PBDEs in the Baltic Sea's predominant specie, the blue mussel. The main focus was on the conjugation of OH-PBDEs with lipophilic moieties (e.g., fatty acids) and the potential role this transformation mechanism may have in heavily exposed mussels in nature. Analytical methods were developed to accurately determine the concentrations of these conjugates in blue mussels collected on different occasions during the summer in a coastal area of the Baltic proper. The measured concentrations of conjugated OH-PBDEs were compared to those of the unconjugated parent compounds, and it was found that in some cases, the levels of the conjugated derivatives can be equal or even higher than the levels of the unconjugated OH-PBDEs. This is, to our knowledge, the first study on lipid-soluble OH-PBDE conjugates, and the first study to investigate the occurrence of such conjugates of halogenated phenolic compounds in environmentally exposed mussels. The mussels were also found to contain hydrolysable water-soluble derivatives of OH-PBDEs (such as e.g., glucuronic acid and/or sulfate conjugates etc.). These were tentatively determined to be of lower concentration (by up to an order of magnitude) than that of the OH-PBDEs which were conjugated with lipophilic moieties.
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| 9. |
- Lundstedt-Enkel, Katrin, et al.
(författare)
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Modeling Relationships between Baltic Sea Herring (Clupea harengus) Biology and Contaminant Concentrations Using Multivariate Data Analysis
- 2010
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:23, s. 9018-9023
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Tidskriftsartikel (refereegranskat)abstract
- Baltic Sea herring (Clupea harengus) is a pelagic, zoo-planktivorous fish and young (2-5 years old) individuals of this species are sampled annually in the Swedish marine monitoring program. This study determined concentrations of organochlorines (OCs) and brominated flame retardants (BFRs) in dorsal muscle from herring (n = 60) of varying age (2-13 years), weight (25-200 g), and body length (16-29 cm) caught at three locations in the Swedish part of the Baltic Proper. In order to ensure that the fish biclogy was as varied as possible, though still similar from all sampling sites, the fish to be chemically analyzed were selected from a large number of fish with determined biology using Multivariate Design. In statistical evaluation of the data, univariate and multivariate data analysis techniques, e.g. principal components analysis (PCA), partial least-squares regression (PLS), and orthogonal PLS (OPLS), were used. The results showed that the fish are exposed to a cocktail of contaminants and levels are presented. Significant OPLS models were found for all biological variables versus concentrations of OCs and BFRs, showing that fish biology covaries with fish contaminant concentrations. Correlation coefficients were as high as 0.98 for e.g. beta HCH concentration (wet weight) versus the lipid content. Lastly, the DC concentrations in herring muscle were modeled against the BFR concentrations to determine whether concentrations of either could be used to predict the other. It was found that OPLS models allowed BFR concentrations to be predicted from OC concentrations with high, but varying, accuracy (R-2 Ys between 0.93 to 0.75). Thus, fish biology and contaminant concentrations are interwoven, and fish biological parameters can be used to calculate (predict) contaminant concentrations. It is also possible to predict the BFR concentrations in an individual fish from its concentrations of OCs with very high accuracy.
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| 10. |
- Löfstrand, Karin, et al.
(författare)
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Brominated phenols, anisoles, and dioxins present in blue mussels from the Swedish coastline
- 2010
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Ingår i: Environmental Science and Pollution Research. - : Springer Science and Business Media LLC. - 0944-1344 .- 1614-7499. ; 17:8, s. 1460-1468
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Naturally occurring hydroxylated polybrominated diphenyl ethers (OH-PBDEs), their methoxylated counterparts (MeO-PBDEs), and polybrominated dibenzo-p-dioxins (PBDDs), together with their potential precursors polybrominated phenols (PBPs) and polybrominated anisoles (PBAs), were analyzed in blue mussels (Mytilus edulis) gathered along the east coast (bordering the Baltic Sea) and west coast of Sweden (bordering the North Sea). Brown algae (Dictyosiphon foenicolaceus) and cyanobacteria (Nodularia spumigena) from the Baltic Sea, considered to be among the primary producers of these compounds, were also analyzed for comparison. Materials and methods The samples were liquid–liquid extracted, separated into a phenolic and a neutral fraction, and subsequently analyzed by gas chromatography–mass spectrometry (GS-MS). Results and discussion The levels of OH-PBDEs, MeO-PBDEs and PBDDs were significantly higher in Baltic Sea mussels than in those from the west coast, whereas the levels of PBPs and PBAs displayed the opposite pattern. The blue mussels from the Baltic Sea contained high levels of all analyzed substances, much higher than the levels of, e.g., polybrominated diphenyl ethers. In addition, the GC-MS chromatogram of the phenolic fraction of the west coast samples was dominated by four unknown peak clusters, three of which were tentatively identified as dihydroxy-PBDEs and the other as a hydroxylated-methyl-tetraBDE. Conclusions Clearly, all of the compounds analyzed are natural products, both in the Baltic and the North Sea. However, the geographical differences in composition may indicate different origin, e.g., due to differences in the occurrence and/or abundance of various algae species along these two coasts or possibly a more extensive dilution on the west coast.
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