Activation of Human Stearoyl-Coenzyme A Desaturase 1 Contributes to the Lipogenic Effect of PXR in HepG2 Cells

The pregnane X receptor (PXR) was previously known as a xenobiotic receptor. Several recent studies suggested that PXR also played an important role in lipid homeostasis but the underlying mechanism remains to be clearly defined. In this study, we found that rifampicin, an agonist of human PXR, induced lipid accumulation in HepG2 cells. Lipid analysis showed the total cholesterol level increased. However, the free cholesterol and triglyceride levels were not changed. Treatment of HepG2 cells with rifampicin induced the expression of the free fatty acid transporter CD36 and ABCG1, as well as several lipogenic enzymes, including stearoyl-CoA desaturase-1 (SCD1), long chain free fatty acid elongase (FAE), and lecithin-cholesterol acyltransferase (LCAT), while the expression of acyl:cholesterol acetyltransferase(ACAT1) was not affected. Moreover, in PXR over-expressing HepG2 cells (HepG2-PXR), the SCD1 expression was significantly higher than in HepG2-Vector cells, even in the absence of rifampicin. Down-regulation of PXR by shRNA abolished the rifampicin-induced SCD1 gene expression in HepG2 cells. Promoter analysis showed that the human SCD1 gene promoter is activated by PXR and a novel DR-7 type PXR response element (PXRE) response element was located at -338 bp of the SCD1 gene promoter. Taken together, these results indicated that PXR activation promoted lipid synthesis in HepG2 cells and SCD1 is a novel PXR target gene. © 2013 Zhang et al

New hydroxylated metabolites of 4-monochlorobiphenyl in whole poplar plants

Two new monohydroxy metabolites of 4-monochlorobiphenyl (CB3) were positively identified using three newly synthesized monohydroxy compounds of CB3: 2-hydroxy-4-chlorobiphenyl (2OH-CB3), 3-hydroxy-4-chlorobiphenyl (3OH-CB3) and 4-hydroxy-3-chlorobiphenyl (4OH-CB2). New metabolites of CB3, including 2OH-CB3 and 3OH-CB3, were confirmed in whole poplars (Populus deltoides × nigra, DN34), a model plant in the application of phytoremediation. Furthermore, the concentrations and masses of 2OH-CB3 and 3OH-CB3 formed in various tissues of whole poplar plants and controls were measured. Results showed that 2OH-CB3 was the major product in these two OH-CB3s with chlorine and hydroxyl moieties in the same phenyl ring of CB3. Masses of 2OH-CB3 and 3OH-CB3 in tissues of whole poplar plants were much higher than those in the hydroponic solution, strongly indicating that the poplar plant itself metabolizes CB3 to both 2OH-CB3 and 3OH-CB3. The total yield of 2OH-CB3 and 3OH-CB3, with chlorine and hydroxyl in the same phenyl ring of CB3, was less than that of three previously found OH-CB3s with chlorine and hydroxyl in the opposite phenyl rings of CB3 (2'OH-CB3, 3'OH-CB3, and 4'OH-CB3). Finally, these two newly detected OH-CB3s from CB3 in this work also suggests that the metabolic pathway was via epoxide intermediates. These five OH-CB3s clearly showed the complete metabolism profile from CB3 to monohydroxylated CB3. More importantly, it's the first report and confirmation of 2OH-CB3 and 3OH-CB3 (new metabolites of CB3) in a living organism

Ab initio prediction of Boron compounds arising from Borozene: Structural and electronic properties

Structure and electronic properties of two unusual boron clusters obtained by fusion of borozene rings has been studied by means of first principles calculations, based on the generalized-gradient approximation of the density functional theory, and the semiempirical tight-binding method was used for the transport calculations. The role of disorder has also been considered with single vacancies and substitutional atoms. Results show that the pure boron clusters are topologically planar and characterized by (3c-2e) bonds, which can explain, together with the aromaticity (estimated by means of NICS), the remarkable cohesive energy values obtained. Such feature makes these systems competitive with the most stable boron clusters to date. On the contrary, the introduction of impurities compromises stability and planarity in both cases. The energy gap values indicate that these clusters possess a semiconducting character, while when the larger system is considered, zero-values of the density of states are found exclusively within the HOMO-LUMO gap. Electron transport calculations within the Landauer formalism confirm these indications, showing semiconductor-like low bias differential conductance for these stuctures. Differences and similarities with Carbon clusters are highlighted in the discussion.Comment: 10 pages, 2 tables, 5 figure

B12Hn and B12Fn: planar vs icosahedral structures

Using density functional theory and quantum Monte Carlo calculations, we show that B12Hn and B12Fn (n = 0 to 4) quasi-planar structures are energetically more favorable than the corresponding icosahedral clusters. Moreover, we show that the fully planar B12F6 cluster is more stable than the three-dimensional counterpart. These results open up the possibility of designing larger boron-based nanostructures starting from quasi-planar or fully planar building blocks

Selective Synthesis of Fe2O3 and Fe3O4 Nanowires Via a Single Precursor: A General Method for Metal Oxide Nanowires

Hematite (α-Fe2O3) and magnetite (Fe3O4) nanowires with the diameter of about 100 nm and the length of tens of micrometers have been selectively synthesized by a microemulsion-based method in combination of the calcinations under different atmosphere. The effects of the precursors, annealing temperature, and atmosphere on the morphology and the structure of the products have been investigated. Moreover, Co3O4 nanowires have been fabricated to confirm the versatility of the method for metal oxide nanowires

Systematic Functional Analysis of Bicaudal-D Serine Phosphorylation and Intragenic Suppression of a Female Sterile Allele of BicD

Protein phosphorylation is involved in posttranslational control of essentially all biological processes. Using mass spectrometry, recent analyses of whole phosphoproteomes led to the identification of numerous new phosphorylation sites. However, the function of most of these sites remained unknown. We chose the Drosophila Bicaudal-D protein to estimate the importance of individual phosphorylation events. Being involved in different cellular processes, BicD is required for oocyte determination, for RNA transport during oogenesis and embryogenesis, and for photoreceptor nuclei migration in the developing eye. The numerous roles of BicD and the available evidence for functional importance of BicD phosphorylation led us to identify eight phosphorylation sites of BicD, and we tested a total of 14 identified and suspected phosphoserine residues for their functional importance in vivo in flies. Surprisingly, all these serines turned out to be dispensable for providing sufficient basal BicD activity for normal growth and development. However, in a genetically sensitized background where the BicDA40V protein variant provides only partial activity, serine 103 substitutions are not neutral anymore, but show surprising differences. The S103D substitution completely inactivates the protein, whereas S103A behaves neutral, and the S103F substitution, isolated in a genetic screen, restores BicDA40V function. Our results suggest that many BicD phosphorylation events may either be fortuitous or play a modulating function as shown for Ser103. Remarkably, amongst the Drosophila serines we found phosphorylated, Ser103 is the only one that is fully conserved in mammalian BicD

Common genetic variation in the Estrogen Receptor Beta (ESR2) gene and osteoarthritis: results of a meta-analysis

Background: The objective of this study was to examine the relationship between common genetic variation of the ESR2 gene and osteoarthritis.Methods: In the discovery study, the Rotterdam Study-I, 7 single nucleotide polymorphisms (SNPs) were genotyped and tested for association with hip (284 cases, 2772 controls), knee (665 cases, 2075 controls), and hand OA (874 cases, 2184 controls) using an additive model. In the replication stage one SNP (rs1256031) was tested in an additional 2080 hip, 1318 knee and 557 hand OA cases and 4001, 2631 and 1699 controls respectively. Fixed- and random-effects meta-analyses were performed over the complete dataset including 2364 hip, 1983 knee and 1431 hand OA cases and approximately 6000 controls.Results: The C allele of rs1256031 was associated with a 36% increased odds of hip OA in women of the Rotterdam Study-I (OR 1.36, 95% CI 1.08-1.70, p = 0.009). Haplotype analysis and analysis of knee- and hand OA did not give additional information. With the replication studies, the meta-analysis did not show a significant effect of this SNP on hip OA in the total population (OR 1.06, 95% CI 0.99-1.15, p = 0.10). Stratification according to gender did not change the results. In this study, we had 80% power to detect an odds ratio of at least 1.14 for hip OA (α = 0.05).Conclusion: This study showed that common genetic variation in the ESR2 gene is not likely to influence the risk of osteoarthritis with effects smaller than a 13% increase

A Comprehensive Analysis of the Dynamic Biological Networks in HCV Induced Hepatocarcinogenesis

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, which is closely related to hepatitis C and cirrhosis. The molecular mechanisms underlying the hepatocarcinogenesis induced by HCV infection remain clarified from a standpoint of systems biology. By integrating data from protein-protein interactions, transcriptional regulation, and disease related microarray analysis, we carried out a dynamic biological network analysis on the progression of HCV induced hepatocarcinogenesis, and systematically explored the potentially disease-related mechanisms through a network view. The dysfunctional interactions among proteins and deregulatory relationships between transcription factors and their target genes could be causes for the occurrence and progression of this disease. The six pathologically defined disease stages in the development and progression of HCC after HCV infection were included in this study. We constructed disease-related biological networks for each disease stage, and identified progression-related sub-networks that potentially play roles in the developmental stage of the corresponding disease and participate in the later stage of cancer progression. In addition, we identified novel risk factors related to HCC based on the analysis of the progression-related sub-networks. The dynamic characteristics of the network reflect important features of the disease development and progression, which provide important information for us to further explore underlying mechanisms of the disease