Effect of Bitis gabonica and Dendroaspis angusticeps snake venoms on apoptosis-related genes in human thymic epithelial cells.

BACKGROUND: Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from Bitis gabonica and Dendroaspis angusticeps. METHODS: Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 µg/mL (as used in previous TaqMan Array study). Gene expressional changes restricted to apoptosis were assayed by TaqMan Array (Human Apoptosis Plate). RESULTS: The most prominent gene expressional changes were shown by CASP5 (≈ 2.5 million-fold, confirmed by dedicated quantitative polymerase chain reaction) and CARD9 (0.016-fold) for B. gabonica, and BIRC7 (6.46-fold) and CASP1 (0.30-fold) for D. angusticeps. CONCLUSION: The observed apoptotic environment suggests that pyroptosis may be the dominant pathway through which B. gabonica and D. angusticeps snake venoms trigger thymic epithelial apoptosis following envenomation.

Effect of Bitis gabonica and Dendroaspis angusticeps snake venoms on apoptosis-related genes in human thymic epithelial cells

Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from Bitis gabonica and Dendroaspis angusticeps. Methods: Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 μg/mL (as used in previous TaqMan Array study). Gene expressional changes restricted to apoptosis were assayed by TaqMan Array (Human Apoptosis Plate). Results: The most prominent gene expressional changes were shown by CASP5 (≈ 2.5 million-fold, confirmed by dedicated quantitative polymerase chain reaction) and CARD9 (0.016-fold) for B. gabonica, and BIRC7 (6.46-fold) and CASP1 (0.30-fold) for D. angusticeps. Conclusion: The observed apoptotic environment suggests that pyroptosis may be the dominant pathway through which B. gabonica and D. angusticeps snake venoms trigger thymic epithelial apoptosis following envenomation.(AU)

Formation, Characterization, and Reactivity of a Nonheme Oxoiron(IV) Complex Derived from the Chiral Pentadentate Ligand asN4Py.

The chiral pentadentate low-spin (S = 1) oxoiron(IV) complex [FeIV(O)(asN4Py)]2+ (2) was synthesized and spectroscopically characterized. Its formation kinetics, reactivity, and (enantio)selectivity in an oxygen-atom-transfer reaction was investigated in detail and compared to a similar pentadentate ligand-containing system.

Biological and computational evaluation of resveratrol inhibitors against Alzheimer's disease.

It has been reported that beta amyloid induces production of radical oxygen species and oxidative stress in neuronal cells, which in turn upregulates ß-secretase (BACE-1) expression and beta amyloid levels, thereby propagating oxidative stress and increasing neuronal injury. A series of resveratrol derivatives, known to be inhibitors of oxidative stress-induced neuronal cell death (oxytosis) were biologically evaluated against BACE-1 using homogeneous time-resolved fluorescence (TRF) assay. Correlation between oxytosis inhibitory and BACE-1 inhibitory activity of resveratrol derivatives was statistically significant, supporting the notion that BACE-1 may act as pivotal mediator of neuronal cell oxytosis. Four of the biologically evaluated resveratrol analogs demonstrated considerably higher activity than resveratrol in either assay. The discovery of some "hits" led us to initiate detailed docking studies associated with Molecular Dynamics in order to provide a plausible explanation for the experimental results and understand their molecular basis of action.

Binding and stabilisation effects of glycodendritic compounds with peanut agglutinin.

A number of new polyhydroxy-dendritic structures have been constructed from a few basic modules. The cores were derived from N-tert(butyloxycarbonyl)tris[(propargyloxy)methyl]aminomethane, N,N'-bis-1,3-(tris-(propargyloxymethyl)methyl)-5-(hydroxymethyl)isophthalamide, and N,N',N″-tris-1,3,5-(tris-(propargyloxymethyl)methyl)-1,3,5-benzene tricarboxamide while the terminal groups were derived from ß-azido-galactose and ß-azido-lactose leading to six new glycodendrimeric compounds with up to 63 hydroxyl groups on the periphery. The binding ability of the new compounds to peanut agglutinin (PNA), a galactose recognizing lectin from Arachis hypogaea, was investigated by nano-Isothermal Titration Calorimetry and nano-Differential Scanning Calorimetry. We found that the compounds had stronger stabilising effect on the macromolecules compared to the corresponding sugars. The interaction between lectin and the glycodendrimeric unit is entropically driven with only a low enthalpic contribution. A trend was found with increasing number of carbohydrates that is strongly influenced by the steric constraints of the ligands. Our results indicate the significance of multivalency and size control in the successful design of lectin inhibitors.

Solid-State NMR Study of Paramagnetic Bis(alaninato-κ(2)N,O)copper(II) and Bis(1-amino(cyclo)alkane-1-carboxylato-κ(2)N,O)copper(II) Complexes: Reflection of Stereoisomerism and Molecular Mobility in (13)C and (2)H Fast Magic Angle Spinning Spectra.

Solid-state stereochemistry and mobility of paramagnetic copper(II) complexes formed by aliphatic amino acids (l-alanine, d,l-alanine, 1-amino-2-methyl-alanine) and 1-amino(cyclo)alkane-1-carboxylic acids (alkane = propane, butane, pentane, hexane) as bidentate ligands has been studied by (13)C and (2)H solid-state fast magic angle spinning (MAS) NMR spectroscopy. We examined the prospective method to characterize solid-state paramagnetic compounds in a routine way. Both (13)C and (2)H MAS spectra can distinguish d,l and l,l diastereomers of natural and polydeuterated bis([Dn]alaninato)copper(II) (n = 0, 2, 8) complexes with axial and/or equatorial methyl positions (conformations) primarily due to different Fermi-contact (FC) contributions. The three-bond hyperfine couplings clearly show Karplus-like dependence on the torsional angles which turned out to be a useful assignment aid. Density functional theory calculations of the FC term and crystal structures were also used to aid the final assignments. The correlations obtained for bis(alaninato-κ(2)N,O)copper(II) complexes were successfully used to characterize other complexes. The usefulness of the (2)H MAS spectra of the deuterated complexes was underlined. Even the spectra of the easily exchangeable amine protons contained essential stereochemical information. In the case of a dimer structure of bis(1-aminohexane-1-carboxylato-κ(2)N,O)copper(II) both the (13)C and (2)H resolutions were good enough to confirm the presence of the cis and trans forms in the asymmetric unit. With regard to the internal solid-state motions in the crystal lattice, the obtained quadrupolar tensor parameters were similar for the d,l- and l,l-alaninato isomers and also for the cis-trans forms suggesting similar crystal packing effects, static amine deuterons involved in hydrogen bonding, and fast rotating methyl groups.

Oxidative C-H and C-C bond cleavage by a (2,2'-bipyridine)copper(I) chloride complex.

Acetonitrile is easily oxygenated at ambient reaction conditions to copper(II) oxalate [Cu(bpy)(ox)] n mediated by copper(I) chloride in the presence of 3,5-di-tert-butylcatechol and 2,2'-bipyridine. In the case of other nitriles (e.g., propionitrile), instead, the unusual and selective 1,4-extradiol cleavage of 3,5-di-tert-butylcatechol occurs to give copper(II) tert-butylmaleate [Cu(bma)(bpy)(H2O)]n in good yield.

Catechol oxidase and phenoxazinone synthase activity of a manganese(II) isoindoline complex.

The mononuclear [Mn(6'Me(2)indH)(H(2)O)(2)(CH(3)CN)](ClO(4))(2) (6'Me(2)indH: 1,3-bis(6'-methyl-2'-pyridylimino)isoindoline) complex has been prepared and characterized by various techniques such as elemental analysis, IR, UV-visible and ESR spectroscopy. The title compound was suitable as catalyst for the catalytic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBCH(2)) to 3,5-di-tert-butyl-1,2-benzoquinone (3,5-DTBQ) (catecholase activity), and o-aminophenol (OAPH) to 2-aminophenoxazine-3-one (APX) (phenoxazinone synthase activity) with dioxygen at ambient condition in good yields. Kinetic measurements revealed first-order dependence on the catalyst and dioxygen concentration and saturation type behavior with respect to the corresponding substrate. It was also found that the added triethylamine in both systems accelerates the reaction.