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921.
Subach OM Maltseva DV Shastry A Kolbanovskiy A Klimasauskas S Geacintov NE Gromova ES 《The FEBS journal》2007,274(8):2121-2134
The biologically most significant genotoxic metabolite of the environmental pollutant benzo[a]pyrene (B[a]P), (+)-7R,8S-diol 9S,10R-epoxide, reacts chemically with guanine in DNA, resulting in the predominant formation of (+)-trans-B[a]P-N(2)-dG and, to a lesser extent, (+)-cis-B[a]P-N(2)-dG adducts. Here, we compare the effects of the adduct stereochemistry and conformation on the methylation of cytosine catalyzed by two purified prokaryotic DNA methyltransferases (MTases), SssI and HhaI, with the lesions positioned within or adjacent to their CG and GCGC recognition sites, respectively. The fluorescence properties of the pyrenyl residues of the (+)-cis-B[a]P-N(2)-dG and (+)-trans-B[a]P-N(2)-dG adducts in complexes with MTases are enhanced, but to different extents, indicating that aromatic B[a]P residues are positioned in different microenvironments in the DNA-protein complexes. We have previously shown that the (+)-trans-isomeric adduct inhibits both the binding and methylating efficiencies (k(cat)) of both MTases [Subach OM, Baskunov VB, Darii MV, Maltseva DV, Alexandrov DA, Kirsanova OV, Kolbanovskiy A, Kolbanovskiy M, Johnson F, Bonala R, et al. (2006) Biochemistry45, 6142-6159]. Here we show that the stereoisomeric (+)-cis-B[a]P-N(2)-dG lesion has only a minimal effect on the binding of these MTases and on k(cat). The minor-groove (+)-trans adduct interferes with the formation of the normal DNA minor-groove contacts with the catalytic loop of the MTases. However, the intercalated base-displaced (+)-cis adduct does not interfere with the minor-groove DNA-catalytic loop contacts, allowing near-normal binding of the MTases and undiminished k(cat) values. 相似文献
922.
Alexander Bürkle Graziella Caselli Claudio Franceschi Erminia Mariani Paolo Sansoni Angela Santoni Giancarlo Vecchio Jacek M Witkowski Calogero Caruso 《Immunity & ageing : I & A》2007,4(1):4-8
On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo,
Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed.
In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the
life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different
strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is
essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. 相似文献
923.
Telomeres are DNA-protein complexes at the ends of chromosomes that control genomic integrity but appear to become shorter with age and stress. To test whether stress causes telomere attrition, we exposed the offspring of wild-caught house mice (Mus musculus) to stressful conditions and examined the changes in telomere length over six months. We found that females exposed to males and reproductive stress (either with or without crowding) had significantly shorter telomeres than controls, and males exposed to crowding stress had shorter telomeres than males that were not crowded. Our results indicate that stress alters telomere dynamics, causing attrition and hindering restoration, and these effects are sex dependent. Telomeres may thus provide a biomarker for assessing an individual's cumulative exposure or ability to cope with stressful conditions. 相似文献
924.
Lena S. Sal Finn L. Aachmann Hwa-Young Kim Vadim N. Gladyshev Alexander Dikiy 《Biomolecular NMR assignments》2007,1(1):131-133
Isotopically labeled, 15N and 15N/13C forms of recombinant methionine-r-sulfoxide reductase 1 (MsrB1, SelR) from Mus musculus were produced, in which catalytic selenocysteine was replaced with cysteine. We report here the 1H, 15N and 13C NMR assignment of the reduced form of this mammalian protein. 相似文献
925.
Acid-sensing ion channels (ASIC) are ligand-gated cation channels that are highly expressed in peripheral sensory and central neurons. ASIC are transiently activated by decreases in extracellular pH and are thought to play important roles in sensory perception, neuronal transmission, and excitability, and in the pathology of neurological conditions, such as brain ischemia. We demonstrate here that the heavy metals Ni(2+) and Cd(2+) dose-dependently inhibit ASIC currents in hippocampus CA1 neurons and in Chinese hamster ovary (CHO) cells heterologously expressing these channels. The effects of both Ni(2+) and Cd(2+) were voltage-independent, fast, and reversible. Neither metal affected activation and desensitization kinetics but rather decreased pH-sensitivity. Moreover, distinct ASIC isoforms were differentially inhibited by Ni(2+) and Cd(2+). External application of 1 mM Ni(2+) rapidly inhibited homomeric ASIC1a and heteromeric ASIC1a/2a channels without affecting ASIC1b, 2a, and ASIC3 homomeric channels and ASIC1a/3 and 2a/3 heteromeric channels. In contrast, external Cd(+) (1 mM) inhibited ASIC2a and ASIC3 homomeric channels and ASIC1a/2a, 1a/3, and 2a/3 heteromeric channels but not ASIC1a homomeric channels. The acid-sensing current in isolated rat hippocampus CA1 neurons, thought to be carried primarily by ASIC1a and 1a/2a, was inhibited by 1 mM Ni(2+). The current study identifies ASIC as a novel target for the neurotoxic heavy metals Cd(2+) and Ni(2+). 相似文献
926.
Fountain KJ Kloss A Garibyan I Blitshteyn B Brezzani A Kyostio-Moore S Zuk A Sacchiero R Cohen AS 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,846(1-2):245-251
An ion exchange high performance liquid chromatography method was developed for determining creatinine levels in both mouse and rat serum samples. Separation of creatinine from other serum components was achieved in 10 min using a 100 x 4.1-mm, 10 microm strong cation exchange column following acetonitrile precipitation of serum proteins. Incorporation of a guard cartridge placed in-line prior to the analytical column was employed to prevent interference from compounds used in renal disease animal trials. Creatinine levels in normal and diseased animals were accurately determined in the 0.01-10 mg/dL range, and average recovery of the method was approximately 85% for both mouse and rat serum. Addition of 0.5-1.0% acetic acid to the acetonitrile used for protein precipitation significantly improved creatinine recovery to above 97% in mouse serum. The method was used for routine preclinical diagnosis of rat and mouse model renal function, and for the evaluation of renal disease treatment efficacy. 相似文献
927.
Proposed minimum reporting standards for chemical analysis 总被引:4,自引:0,他引:4
Lloyd W. Sumner Alexander Amberg Dave Barrett Michael H. Beale Richard Beger Clare A. Daykin Teresa W.-M. Fan Oliver Fiehn Royston Goodacre Julian L. Griffin Thomas Hankemeier Nigel Hardy James Harnly Richard Higashi Joachim Kopka Andrew N. Lane John C. Lindon Philip Marriott Andrew W. Nicholls Michael D. Reily John J. Thaden Mark R. Viant 《Metabolomics : Official journal of the Metabolomic Society》2007,3(3):211-221
There is a general consensus that supports the need for standardized reporting of metadata or information describing large-scale
metabolomics and other functional genomics data sets. Reporting of standard metadata provides a biological and empirical context
for the data, facilitates experimental replication, and enables the re-interrogation and comparison of data by others. Accordingly,
the Metabolomics Standards Initiative is building a general consensus concerning the minimum reporting standards for metabolomics
experiments of which the Chemical Analysis Working Group (CAWG) is a member of this community effort. This article proposes
the minimum reporting standards related to the chemical analysis aspects of metabolomics experiments including: sample preparation,
experimental analysis, quality control, metabolite identification, and data pre-processing. These minimum standards currently
focus mostly upon mass spectrometry and nuclear magnetic resonance spectroscopy due to the popularity of these techniques
in metabolomics. However, additional input concerning other techniques is welcomed and can be provided via the CAWG on-line
discussion forum at or . Further, community input related to this document can also be provided via this electronic forum.
The contents of this paper do not necessarily reflect any position of the Government or the opinion of the Food and Drug Administration
Sponsor: Metabolomics Society http://www.metabolomicssociety.org/
Reference: http://msi-workgroups.sourceforge.net/bio-metadata/reporting/pbc/
http://msi-workgroups.sourceforge.net/chemical-analysis/
Version: Revision: 5.1
Date: 09 January, 2007 相似文献
928.
Milov AD Tsvetkov YD Gorbunova EY Mustaeva LG Ovchinnikova TV Handgraaf JW Raap J 《化学与生物多样性》2007,4(6):1243-1255
Zervamicin is a voltage-gated ion-channel-forming peptide. Channels are generally considered to be formed by first insertion of amphipathic molecules into the phospholipid bilayer, followed by self-assembly of a variable number of transmembrane helices. We have studied the length of the peptide structure to address the question whether this peptide is long enough to span the phospholipid bilayer. The pulsed electron-electron double resonance (PELDOR) spectroscopic technique was used to determine the length of the helical molecule in membrane-mimicking solvents. This was achieved from the distance-related dipole-dipole interaction between spin labels, which were located at both ends of the linear peptide chain. The data were obtained by using samples of frozen glassy solutions of MeOH, MeOH/toluene, and MeOH/CHCl(3). Contributions of inter- and intramolecular interactions of spin labels were separated to analyze the intramolecular interaction and the distance distribution function between the labels. It is shown that the main maximum of the distribution functions is located at a distance of ca. 3.3 nm, and this distance appears to be only slightly dependent on the solvent composition. The distribution function was observed to narrow after addition of either CHCl(3) or toluene to MeOH. This effect is rationalized in terms of a decreased mobility of the terminal amino acid residues. By molecular-dynamics simulations, it was shown that the conformation, corresponding with the predominant distance found by PELDOR, agrees well with the mixed alpha/3(10)-helical that was previously determined by NMR. However, in the case toluene was added to the MeOH solution to further increase the hydrophobicity of the environment of the membrane-active peptide, the distribution function gives rise to a minor fraction (7-8%) with a distance of 4.2 nm. This distance corresponds most likely to the more extended 2(7)-helix structure. 相似文献
929.
Milov AD Samoilova MI Tsvetkov YD Jost M Peggion C Formaggio F Crisma M Toniolo C Handgraaf JW Raap J 《化学与生物多样性》2007,4(6):1275-1298
Three analogs of alamethicin F50/5, labelled with the TOAC (='2,2,6,6-tetramethylpiperidin-1-oxyl-4-amino-4-carboxylic acid') spin label at positions 1 (Alm1), 8 (Alm8), and 16 (Alm16), resp., were studied by Electron-Spin-Resonance (ESR) and Pulsed Electron-Electron Double-Resonance (PELDOR) techniques in solvents of different polarity to investigate the self-assembly of amphipathic helical peptides in membrane-mimicking environments. In polar solvents, alamethicin forms homogeneous solutions. In the weakly polar chloroform/toluene 1 : 1 mixture, however, this peptide forms aggregates that are detectable at 293 K by ESR in liquid solution, as well as by PELDOR in frozen, glassy solution at 77 K. In liquid solution, free alamethicin molecules and their aggregates show rotational-mobility correlation times tau(r) of 0.87 and 5.9 ns, resp. Based on these values and analysis of dipole-dipole interactions of the TOAC labels in the aggregates, as determined by PELDOR, the average number N of alamethicin molecules in the aggregates is estimated to be less than nine. A distance-distribution function between spin labels in the supramolecular aggregate was obtained. This function exhibits two maxima: a broad one at a distance of 3.0 nm, and a wide one at a distance of ca. 7 nm. A molecular-dynamics (MD)-based model of the aggregate, consisting of two parallel tetramers, each composed of four molecules arranged in a 'head-to-tail' fashion, is proposed, accounting for the observed distances and their distribution. 相似文献
930.
Pshezhetsky AV Fedjaev M Ashmarina L Mazur A Budman L Sinnett D Labuda D Beaulieu JF Ménard D Nifant'ev I Levy E 《Proteomics》2007,7(13):2201-2215
Human colorectal carcinoma (Caco-2) cells undergo in culture spontaneous enterocytic differentiation, characterized by polarization and appearance of the functional apical brush border membrane. To provide insights into the biology of differentiation, we have performed a comparative proteomic analysis of the plasma membranes from proliferating cells (PCs) and the apical membranes from differentiated cells (DCs). Proteins were resolved by SDS-PAGE, in-gel digested and analyzed by RP-LC and MS/MS. Alternatively, proteins were digested in solution, and tryptic peptides were labeled with isotopic tags and analyzed by 2-D LC followed by MS/MS. Among the 1125 proteins identified in both proteomes, 76 were found to be significantly increased in the membranes of DCs and 61 were increased in PCs. Majority of the proteins increased in the apical membranes were metabolic enzymes, proteins involved in the maintenance of cellular structure, transmembrane transporters, and proteins regulating vesicular transport. In contrast, majority of the proteins increased in the membranes of PCs were involved in gene expression, protein synthesis, and folding. Both groups contained many novel proteins with yet to be identified functions, which could provide potential new markers of the intestinal cells or of colorectal cancer. 相似文献