Type 1 IFN inhibits the growth factor deprived apoptosis of cultured human aortic endothelial cells and protects the cells from chemically induced oxidative cytotoxicity

It has been shown that the genesis of atherosclerotic lesions is resulted from the injury of vascular endothelial cells and the cell damage is triggered by oxygen radicals generated from various tissues. Human vascular endothelial cells can survive and proliferate depending on growth factors such as VEGF or basic FGF and are induced apoptosis by the deprivation of growth factor or serum. It was found that type 1 IFN inhibits the growth factor deprived cell death of human aortic endothelial cells (HAEC) and protects the cells from chemically induced oxidative cytotoxicity. The anti‐apoptotic effects of type 1 IFN were certified by flow cytometry using annexin‐V‐FITC/PI double staining and cell cycle analysis, fluorescence microscopy using Hoechst33342 and PI, colorimetric assay for caspase‐3 activity, p53 and bax mRNA expressions, and cell counts. It was considered that IFN‐β inhibits the executive late stage apoptosis from the results of annexin‐V‐FITC/PI double staining and the inhibition of caspase‐3 activity, and that the anti‐apoptotic effect might be owing to the direct inhibition of the apoptotic pathway mediated by p53 from the transient down‐regulation of bax mRNA expression. Whereas, type 1 IFN protected the cells from the oxidative cytotoxicity induced by tertiary butylhydroperoxide (TBH) under the presence of Ca²⁺. The effects of IFN‐β is more potent inhibitor of cell death than IFN‐α. These results indicate that type 1 IFN, especially IFN‐β may be useful for the diseases with vascular endothelium damage such as atherosclerosis or restenosis after angioplasty as a medical treatment or a prophylactic. J. Cell. Biochem. 113: 3823–3834, 2012. © 2012 Wiley Periodicals, Inc.     

The effects of moderate-intensity gradient static magnetic fields on nerve conduction

Whether exposure to static magnetic fields (SMF) for medical applications poses a therapeutic benefit or a health hazard is at the focus of current debate. As a peripheral nerve model for studies of the SMF effects, we have investigated whether exposure of in vitro frog sciatic nerve fibers to moderate-intensity gradient SMF up to 0.7 T modulates membrane excitation and refractory processes. We measured the changes in the amplitudes of the electrically evoked compound action potentials for three groups: a control group without SMF exposure and two exposed groups with continuous inhomogeneous exposure to maximum flux densities (B(max)) of 0.21 and 0.7 T SMF for 6 h. The values of the nerve conduction velocity of C fibers were significantly reduced by B(max) of 0.7 T SMF during the 4- to 6-h exposure period but not by B(max) of 0.21 T SMF during the entire exposure period of 6 h, relative to the unexposed control. From these findings, we speculate that exposure to moderate-intensity gradient SMF may attenuate pain perception because the C fibers are responsible for pain transmission. Although the mechanistic reasons for this decrease have yet to be clarified, SMF could affect the behavior of some types of ion channels associated with C fibers.     

Simultaneous analytical method for urinary metabolites of organophosphorus compounds and moth repellents in general population

An analytical method was developed for simultaneous measurement of urinary metabolites in the general population exposed to organophosphorus compounds (insecticides, flame retardants and plasticizers) and moth repellents used in Japanese households. Fifteen metabolites, dimethylphosphate, dimethylthiophosphate, diethylphosphate, diethylthiophosphate, di-n-butylphosphate, diphenylphosphate, bis(2-ethylhexyl)phosphate, 2-isopropyl-6-methyl-4-pyrimidinol, 3,5,6-trichloro-2-pyridinol, 3-methyl-4-(methylthio)phenol, 3-methyl-4-nitrophenol, 2,4-dichlorophenol, 2,5-dichlorophenol, 1-naphthol and 2-naphthol, were extracted from hydrolyzed urine by using a sorbent (hydroxylated polystyrene-divinylbenzene copolymers), and then desorbed with methylacetate and acetonitrile, concentrated, and after transformation to their tert-butyldimethylsilyl derivatives, analyzed by gas chromatography/mass spectrometry in the electron impact ionization mode. They could be determined accurately and precisely (quantification limits: 0.8-4 μg/l). The collected urine samples could be stored for up to 1 month at -20°C in a freezer.     

Suppressors: Determinants of Specificity Produced by Plant Pathogens

Plant pathogens secrete suppressors that delay or prevent thehost defense responses, with resultant conditioning of hostcells such that they become susceptible even to avirulent ornon-pathogenic microorganisms. Suppressors have been characterizedas glycoproteins, glycopeptides, peptides and anionic and nonanionicglucans. A suppressor itself is non-toxic to plant cells and,thus, it can be distinguished from host-specific toxins producedby certain pathogens. Suppressors disturb fundamental functionsof host plasma membranes. For example, the suppressor from apea pathogen, Mycosphaerella pinodes, inhibits both the ATPaseactivity and polyphosphoinositide metabolism in pea plasma membranes,causing the temporary suppression of the signal-transductionpathway that leads to the expression of defense genes, whichencode key enzymes in the biosynthetic pathway to phytoalexin.In this review, evidence for the role of suppressors in thedetermination of plant host-parasite specificity is summarized. ³Present address: Plant Pathology Laboratory, School of Agriculture,Nagoya University, Chikusa, Nagoya, 464-01 Japan     

Molecular modeling of human acidic mammalian chitinase in complex with the natural-product cyclopentapeptide chitinase inhibitor argifin

Human acidic mammalian chitinase (hAMCase) is an attractive target for developing anti-asthma medications. We used a variety of computational methods to investigate the interaction between hAMCase and the natural-product cyclopentapeptide chitinase inhibitor argifin. The three-dimensional structure of hAMCase was first constructed using homology modeling. The interaction mode and binding free energy between argifin and hAMCase were then examined by the molecular-docking calculation and the molecular mechanics Poisson–Boltzmann surface area method combined with molecular dynamics simulation, respectively. The results suggested that argifin binds to hAMCase in a similar fashion to the interaction mode observed in the crystal structure of argifin-human chitotriosidase complex, and possesses inhibitory activity against hAMCase in the micromolar range. We further designed argifin derivatives expected to be selective for hAMCase.