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11.
Patricia A. Thompson Karine C. Gauthier Alan W. Varley Richard L. Kitchens 《Journal of lipid research》2010,51(9):2672-2685
Macrophages play important roles in both lipid metabolism and innate immunity. We show here that macrophage ATP-binding cassette transporter A1 (ABCA1), a transporter known for its ability to promote apolipoprotein-dependent cholesterol efflux, also participates in the removal of an immunostimulatory bacterial lipid, lipopolysaccharide (LPS). Whereas monocytes require an exogenous lipoprotein acceptor to remove cell-associated LPS, macrophages released LPS in the absence of an exogenous acceptor by a mechanism that was driven, in part, by endogenous apolipoprotein E (apoE). Agents that increased ABCA1 expression increased LPS efflux from wild-type but not ABCA1-deficient macrophages. Preexposure of peritoneal macrophages to LPS for 24 h increased the expression of ABCA1 and increased LPS efflux with a requirement for exogenous apolipoproteins due to suppression of endogenous apoE production. In contrast, LPS preconditioning of ABCA1-deficient macrophages significantly decreased LPS efflux and led to prolonged retention of cell-surface LPS. Although the initial response to LPS was similar in wild-type and ABCA1-deficient macrophages, LPS-induced tolerance was greater and more prolonged in macrophages that lacked ABCA1. Our results define a new role for macrophage ABCA1 in removing cell-associated LPS and restoring normal macrophage responsiveness. 相似文献
12.
Effect of vitamin B-12 deprivation on the rates of synthesis and degradation of rat liver fatty acid synthetase 总被引:1,自引:0,他引:1
E P Frenkel R L Kitchens J M Johnston R Frenkel 《Archives of biochemistry and biophysics》1974,162(2):607-613
To characterize the basis for the increased hepatic fatty acid synthetase activity in vitamin B-12 deprivation, the content and rates of synthesis and degradation for the enzyme were determined. Animals were in a dietary steady state on normal chow or a B-12-deprived diet; animals on the latter diet were further divided into a “supplemented” group given B-12 and those “B-12-deprived.” The B-12-deprived animals had tissue B-12 depletion. Both total and specific activity of fatty acid synthetase were increased in the B-12-deprived animals, and this was due to increased enzyme protein. Rates of synthesis and degradation were studied in each group after a pulse of 20 μCi of l-[U-14C]leucine. Radioactivity was determined in the immunoprecipitate of the purified enzyme. Relative rates of synthesis in the B-12-deprived group were increased 8.8-fold over the normal and 3.6-fold over the B-12-supplemented group. Degradation of hepatic fatty acid synthetase was 63 hr () in the normal and 65 hr in the B-12-supplemented group. The in the B-12-deprived group was 35 hr. Degradation rates for the soluble protein pool were not affected by B-12 deprivation. The rate constant for synthesis of hepatic fatty acid synthetase in the B-12-deprived group was 14-fold that of the normal and 6-fold that of the B-12-supplemented animals. Thus, although vitamin B-12 deprivation results in increased rate of degradation of fatty acid synthetase, enzyme synthesis is markedly increased yielding a severalfold net increase in synthetase content and activity. 相似文献
13.
14.
In recent years the Ontario government has been concerned that the proportion of public expenditures devoted to health care is at an all-time high. In addition, the media have devoted considerable attention to specific incidents that may represent inadequate funding of hospital services. To shed light on the debate on health care expenditures we analysed the trend in expenditures of Ontario''s hospital sector in the 1980s in terms of the amount of inputs (e.g., labour) used to produce hospital services (e.g., a patient-day or admission) and after adjustment for general inflation. As in the 1970s the number of inputs grew relatively slowly during the 1980s. Inputs per patient-day grew at an annual rate of 0.46% and inputs per admission at an annual rate of 2.4%. Cost increases were largely accounted for by hospital wage increases; this could have been due to Ontario''s rapidly expanding economy. These findings indicate that Ontario has continued to be successful in containing the number of inputs used in the hospital sector. However, after two decades of substantial success with publicly acceptable cost control, the government faces increased scrutiny as the media and the public focus attention on several areas of perceived inadequate funding in health care services. 相似文献
15.
Paired sequence difference in ribosomal RNAs: evolutionary and phylogenetic implications 总被引:12,自引:1,他引:11
Ribosomal RNAs have secondary structures that are maintained by internal
Watson-Crick pairing. Through analysis of chordate, arthropod, and plant 5S
ribosomal RNA sequences, we show that Darwinian selection operates on these
nucleotide sequences to maintain functionally important secondary
structure. Insect phylogenies based on nucleotide positions involved in
pairing and the production of secondary structure are incongruent with
those constructed on the basis of positions that are not. Furthermore,
phylogeny reconstruction using these nonpairing bases is concordant with
other, morphological data.
相似文献
16.
Mitochondrial gene order is not conserved in arthropods: prostriate and metastriate tick mitochondrial genomes 总被引:25,自引:15,他引:10
The entire mitochondrial genome was sequenced in a prostriate tick, Ixodes
hexagonus, and a metastriate tick, Rhipicephalus sanguineus. Both genomes
encode 22 tRNAs, 13 proteins, and two ribosomal RNAs. Prostriate ticks are
basal members of Ixodidae and have the same gene order as Limulus
polyphemus. In contrast, in R. sanguineus, a block of genes encoding NADH
dehydrogenase subunit 1 (ND1), tRNA(Leu)(UUR), tRNA(Leu)(CUN), 16S rDNA,
tRNA(Val), 12S rDNA, the control region, and the tRNA(Ile) and tRNA(Gln)
have translocated to a position between the tRNA(Glu) and tRNA(Phe) genes.
The tRNA(Cys) gene has translocated between the control region and the
tRNA(Met) gene, and the tRNA(Leu)(CUN) gene has translocated between the
tRNA(Ser)(UCN) gene and the control region. Furthermore, the control region
is duplicated, and both copies undergo concerted evolution. Primers that
flank these rearrangements confirm that this gene order is conserved in all
metastriate ticks examined. Correspondence analysis of amino acid and codon
use in the two ticks and in nine other arthropod mitochondrial genomes
indicate a strong bias in R. sanguineus towards amino acids encoded by
AT-rich codons.
相似文献
17.
Robert J. Fletcher Jr Ellen P. Robertson Rebecca C. Wilcox Brian E. Reichert James D. Austin Wiley M. Kitchens 《Proceedings. Biological sciences / The Royal Society》2015,282(1814)
Understanding dispersal and habitat selection behaviours is central to many problems in ecology, evolution and conservation. One factor often hypothesized to influence habitat selection by dispersers is the natal environment experienced by juveniles. Nonetheless, evidence for the effect of natal environment on dispersing, wild vertebrates remains limited. Using 18 years of nesting and mark–resight data across an entire North American geographical range of an endangered bird, the snail kite (Rostrhamus sociabilis), we tested for natal effects on breeding-site selection by dispersers and its consequences for reproductive success and population structure. Dispersing snail kites were more likely to nest in wetlands of the same habitat type (lacustrine or palustrine) as their natal wetland, independent of dispersal distance, but this preference declined with age and if individuals were born during droughts. Importantly, dispersing kites that bred in natal-like habitats had lower nest success and productivity than kites that did not. These behaviours help explain recently described population connectivity and spatial structure across their geographical range and reveal that assortative breeding is occurring, where birds are more likely to breed with individuals born in the same wetland type as their natal habitat. Natal environments can thus have long-term and large-scale effects on populations in nature, even in highly mobile animals. 相似文献
18.
Floyd TL Koehn BH Kitchens WH Robertson JM Cheeseman JA Stempora L Larsen CP Ford ML 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(4):2033-2041
Donor-reactive memory T cells (Tmem) can play an important role in mediating graft rejection after transplantation. Transplant recipients acquire donor-reactive Tmem not only through prior sensitization with alloantigens but also through previous exposure to environmental pathogens that are cross-reactive with allogeneic peptide-MHC complexes. Current dogma suggests that most, if not all, Tmem responses are independent of the requirement for CD28 and/or CD154/CD40-mediated costimulation to mount a recall response. However, heterogeneity among Tmem is increasingly being appreciated, and one important factor known to impact the function and phenotype of Ag-specific T cell responses is the amount/duration of Ag exposure. Importantly, the impact of Ag exposure on development of costimulation independence is currently unknown. In this study, we interrogated the effect of decreased Ag amount/duration during priming on the ability of donor-reactive Tmem to mediate costimulation blockade-resistant rejection during a recall response after transplantation in a murine model. Recipients possessing donor-reactive Tmem responses that were generated under conditions of reduced Ag exposure exhibited similar frequencies of Ag-specific T cells at day 30 postinfection, but, strikingly, failed to mediate costimulation blockade-resistant rejection after challenge with an OVA-expressing skin graft. Thus, these data demonstrate the amount/duration of Ag exposure is a critical factor in determining Tmem's relative requirement for costimulation during the recall response after transplantation. 相似文献
19.
Li M Oliver E Kitchens KM Vere J Alkan SS Tamiz AP 《Bioorganic & medicinal chemistry letters》2008,18(16):4584-4586
AT-1002 a 6-mer synthetic peptide belongs to an emerging novel class of compounds that reversibly increase paracellular transport of molecules across the epithelial barrier. The aim of this project was to elaborate on the structure-activity relationship of this peptide with the specific goal to replace the P2 cysteine amino acid. Herein, we report the discovery of peptides that exhibit reversible permeability enhancement properties with an increased stability profile. 相似文献
20.
Ligand-mediated induction of thymidylate synthase occurs by enzyme stabilization. Implications for autoregulation of translation 总被引:2,自引:0,他引:2
Kitchens ME Forsthoefel AM Rafique Z Spencer HT Berger FG 《The Journal of biological chemistry》1999,274(18):12544-12547
Thymidylate synthase (TS) is indispensable in the de novo synthesis of dTMP. As such, it has been an important target at which anti-neoplastic drugs are directed. The fluoropyrimidines 5-fluorouracil and 5-fluoro-2'-deoxyuridine are cytotoxic as a consequence of inhibition of TS by the metabolite 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). This inhibition occurs through formation of a stable ternary complex among the enzyme, the nucleotide analog, and the co-substrate N5, N10-methylenetetrahydrofolate. Numerous studies have shown that cellular concentrations of TS undergo about a 2-4-fold induction following treatment with TS inhibitors. An extensive body of in vitro studies has led to the proposal that this induction occurs because of relief of the translational repression brought on by the binding of TS to its own mRNA. In the current study, we have tested several predictions of this autoregulatory translation model. In contrast to expectations, we find that fluoropyrimidines do not cause a change in the extent of ribosome binding to TS mRNA. Furthermore, mutations within the mRNA that abolish its ability to bind TS have no effect on the induction. Finally, enzyme turnover measurements show that the induction is associated with an increase in the stability of the TS polypeptide. Our results, in total, indicate that enzyme stabilization, rather than translational derepression, is the primary mechanism of TS induction by fluoropyrimidines and call into question the general applicability of the autoregulatory translation model. 相似文献