Anti-tumor-initiating effects of phenolic compounds isolated from the bark of Picea jezoensis var. jezoensis

We have previously reported the isolation of nine phenolic compounds including three new flavonostilbenes, jezonocinols A, B, and C, from the MeOH extract of the bark of Picea jezoensis var. jezoensis. Further investigation of the MeOH extract led to the isolation of three new stilbene-type compounds and one new 1,4-benzodioxane-type compound, together with seven known phenolic compounds. These compounds were tested for their inhibitory effects on the activation of (±)-(E)-methyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All compounds tested exhibited potent inhibitory effects on NOR 1 activation. Furthermore, jezonocinol B, the most potent inhibitor of NOR 1 activation, showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO⁻; PN) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter.     

Mechanism of the suppression against <Emphasis Type="SmallCaps">d</Emphasis>-galactosamine-induced hepatic injury by dietary amino acids in rats

To elucidate the mechanism by which dietary amino acids suppress the d-galactosamine (d-GalN)-induced hepatitis, we examined the involvement of Kupffer cells, tumor necrosis factor-α (TNF-α) and apoptosis in the mechanism. In experiment 1, the rats were fed with 10%l-glutamine or 5% glycine diet injected with d-GalN with or without gadolinium chloride (GdCl₃)-pretreatment. The results indicated that these amino acids suppressed the d-GalN-induced elevation of serum transaminase activities, irrespective of GdCl₃-pretreatment. In experiment 2, rats were fed with 10% of l-glutamine, l-serine, l-alanine or l-glutamic acid diets injected with d-GalN. The results demonstrated that all these amino acids suppressed the d-GalN-induced elevation of serum transaminase activities, but that serum TNF-α concentrations and hepatic caspase-3 activities in the rats were not appreciably changed. In conclusion, the suppressive effects of amino acids on d-GalN-induced hepatitis were suggested not to be always mediated by the inhibition of Kupffer cells → TNF-α → apoptosis pathway.     

Glyceraldehyde-3-phosphate dehydrogenase interacts with phosphorylated Akt resulting from increased blood glucose in rat cardiac muscle

Here we describe the interaction of phosphorylated ∼40 kDa protein with phosphorylated Akt which is a serine/threonine kinase resulting from increased blood glucose in rat cardiac muscle. Mass spectrometry analysis revealed that this protein was glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Furthermore, increase in Akt and GAPDH phosporylation and induction of their association were both observed after insulin stimulation in the H9c2 cell line derived from embryonic rat ventricle. Moreover, the activation of GAPDH was upregulated when the GAPDH phosphorylation was increased. Our data suggest that GAPDH phosphorylation and association with Akt by insulin treatment have some bearing on the enhancement of GAPDH activity.

Structured summary

MINT-7891324, MINT-7891304, MINT-7891314: GAPDH (uniprotkb:P04797) physically interacts (MI:0915) with Akt (uniprotkb:P47196) by anti bait coimmunoprecipitation (MI:0006)     

Functional Interaction of Common Allergens and a C-type Lectin Receptor, Dendritic Cell-specific ICAM3-grabbing Non-integrin (DC-SIGN), on Human Dendritic Cells

Fucosylated glycans on pathogens are known to shape the immune response through their interaction with pattern recognition receptors, such as C-type lectin receptors (CLRs), on dendritic cells (DCs). Similar fucosylated structures are also commonly found in a variety of allergens, but their functional significance remains unclear. To test a hypothesis that allergen-associated glycans serve as the molecular patterns in functional interaction with CLRs, an enzyme-linked immunosorbent assay-based binding assay was performed to determine the binding activity of purified allergens and allergen extracts. THP-1 cells and monocyte-derived DCs (MDDCs) were investigated as a model for testing the functional effects of allergen-CLR interaction using enzyme-linked immunosorbent assay, Western blotting, and flow cytometry. Significant and saturable bindings of allergens and allergen extracts with variable binding activities to DC-specific ICAM3-grabbing non-integrin (DC-SIGN) and its related receptor, L-SIGN, were found. These include bovine serum albumin coupled with a common glycoform (fucosylated glycan lacking the α1,3-linked mannose) of allergens and a panel of purified allergens, including BG60 (Cyn dBG-60; Bermuda grass pollen) and Der p2 (house dust mite). The binding activity was calcium-dependent and inhibitable by fucose and Lewis-x trisaccharides (Le^x). In THP-1 cells and human MDDCs, BG60-DC-SIGN interaction led to the activation of Raf-1 and ERK kinases and the induction of tumor necrosis factor-α expression. This effect could be blocked, in part, by Raf-1 inhibitor or anti-DC-SIGN antibodies and was significantly reduced in cells with DC-SIGN knockdown. These results suggest that allergens are able to interact with DC-SIGN and induce tumor necrosis factor-α expression in MDDCs via, in part, Raf-1 signaling pathways.     

Impacts of animal traffic on the Brazilian Amazon parrots (Amazona species) collection of the Quinzinho de Barros Municipal Zoological Park,Brazil, 1986–2007

Eleven species of Amazon parrots (genus Amazona) are known to occur in Brazil, and nest poaching and illegal traffic pose serious conservation threats to these species. When the illegal owners realize these animals are incompatible with their expectations and lifestyle, or when the police arrests traders and owners, these trafficked animals are often considered unfit for release and sent to local zoos and captive breeders. A retrospective survey of animal and necropsy records from 1986 to 2007 was used to evaluate the impacts of animal traffic on the population composition and mortality patterns of Amazon parrots at the Quinzinho de Barros Municipal Zoological Park, Sorocaba, Brazil. Data were obtained for 374 Amazon parrots of ten Brazilian species, and there was evidence that the studied population could be split into two major groups: a majority belonging to the Amazona aestiva species and a minority belonging to the remaining species. In comparison, the animals of the first group were more frequently admitted from traffic‐related origins (98 vs. 75%), had a shorter lifespan (median 301 days vs. 848 days) and a higher mortality within the first year postadmission (54 vs. 37%), were less likely to receive expensive treatments, and were more frequently housed off‐exhibit. On an average, parrots were found to have a short postadmission lifespan (median 356 days), with 92.5% of the birds dying within their first five years in captivity. The paper discusses the difficult dilemmas these incoming traffic‐related animals pose to zoo management and official anti‐traffic policies. Zoo Biol 29:600–614, 2010. © 2010 Wiley‐Liss, Inc.     

A biochemical and genetic study on all non-synonymous single nucleotide polymorphisms of the gene encoding human deoxyribonuclease I potentially relevant to autoimmunity

A reduction of deoxyribonuclease I (DNase I) activity levels in the serum of patients with autoimmune diseases has been reported. The objectives of this study were to clarify genetic and biochemical aspects of 12 non-synonymous SNPs in the human gene (DNASE1), potentially giving rise to an alteration in the in vivo DNase I activity levels. Genotyping of all the non-synonymous SNPs was performed in healthy subjects of three ethnic groups including 15 populations using newly developed methods. Among them, only four SNPs, R-21S, Y95S, G105R, and Q222R were polymorphic in all or some populations; Asian group showed a relatively low genetic diversity of these SNPs. Furthermore, the distribution pattern of the common SNP Q222R was classified into three ethnic groups. The activity levels of the amino acid-substituted DNase I forms derived from SNPs R-21S, G105R, P132A, and P197S were significantly high compared with that of the wild-type; the polymorphic SNPs R-21S and G105R gave rise to a high activity-harboring DNase I isoform. On the other hand, activity levels from Q35H, R85G, V89M, C209Y, Q222R, and A224P were significantly low, but these SNPs, except Q222R, were not distributed in any of the populations. However, since these SNPs may produce potentially low levels of in vivo DNase I activity, a minor allele in each SNP will be served as a genetic risk factor for autoimmune diseases. These findings on non-synonymous SNPs in DNASE1 may provide a biochemical-genetic basis for the clarification of a possible relationship between DNase I and the diseases.