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51.
Cytokines increase transporter in antigen processing-1 expression more rapidly than HLA class I expression in endothelial cells. 总被引:5,自引:0,他引:5
D E Epperson D Arnold T Spies P Cresswell J S Pober D R Johnson 《Journal of immunology (Baltimore, Md. : 1950)》1992,149(10):3297-3301
Transporter in Ag processing-1 (TAP-1, previously called PSF-1 or Ring-4) is an MHC-encoded gene product that is required for efficient association of intracellular peptide Ag with nascent HLA class I H chain and beta 2-microglobulin, thereby permitting assembly and normal surface expression of the class I molecules. TAP-1 is thought to function as a component of a transmembrane pump, that transports cytoplasmically-derived peptides into the lumen of the endoplasmic reticulum where class I molecules assemble. Synthesis and expression of HLA class I molecules is increased in human endothelial cells by IFN-beta, IFN-gamma, and TNF. We report these same cytokines increase TAP-1 expression. As with class I, TAP-1 is also synergistically increased by combinations of TNF with IFN. Interestingly, cytokine-induced increases in TAP-1 mRNA are markedly more rapid than increases in class I mRNA. This rapid increase in TAP-1 mRNA is reflected in a rapid increase in TAP-1 protein. These results demonstrate that TAP-1 synthesis and class I synthesis are regulated in parallel. The rapidity of the cytokine response of TAP-1 compared to class I further suggests that the constitutive level of TAP-1 expression in endothelial cells is not sufficient to support inducible increases in class I expression. 相似文献
52.
BK McNab 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2009,152(1):22-45
The basal rate of metabolism (BMR) in 533 species of birds, when examined with ANCOVA, principally correlates with body mass, most of the residual variation correlating with food habits, climate, habitat, a volant or flightless condition, use or not of torpor, and a highland or lowland distribution. Avian BMR also correlates with migratory habits, if climate and a montane distribution is excluded from the analysis, and with an occurrence on small islands if a flightless condition and migration are excluded. Residual variation correlates with membership in avian orders and families principally because these groups are behaviorally and ecologically distinctive. However, the distinction between passerines and other birds remains a significant correlate of avian BMR, even after six ecological factors are included, with other birds having BMRs that averaged 74% of the passerine mean. This combination of factors accounts for 97.7% of the variation in avian BMR. Yet, migratory species that belong to Anseriformes, Charadriiformes, Pelecaniformes, and Procellariiformes and breed in temperate or polar environments have mass-independent basal rates equal to those found in passerines. In contrast, penguins belong to an order of polar, aquatic birds that have basal rates lower than passerines because their flightless condition depresses basal rate. Passerines dominate temperate, terrestrial environments and the four orders of aquatic birds dominate temperate and polar aquatic environments because their high BMRs facilitate reproduction and migration. The low BMRs of tropical passerines may reflect a sedentary lifestyle as much as a life in a tropical climate. Birds have BMRs that are 30-40% greater than mammals because of the commitment of birds to an expensive and expansive form of flight. 相似文献
53.
Rae L. Russell Philip H. O’Neill L. Elaine Epperson Sandra L. Martin 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2010,180(8):1165-1172
Mammalian hibernation is characterized by profound reductions in body temperature (T
b) and metabolic, heart and respiratory rates. These reductions are characteristic of torpor, which is temporally confined
to winter. Hibernators including ground squirrels are heterothermic in winter, cycling between multiday periods of torpor
with low T
b and brief periods of rewarming. In contrast, ground squirrels remain homeothermic during summer, like non-hibernating mammals.
The transition between the homeothermic and heterothermic phases of the circannual rhythm of hibernation is often overlooked
in hibernation studies. Here, we examined the use of torpor throughout the fall transition in laboratory-housed 13-lined ground
squirrels by recording core body temperature with an implanted data logger. As is typical of laboratory-based hibernation
studies, animals were kept in standard housing prior to being moved into a cold, dark room to simulate natural hibernation
conditions. Significantly, the vast majority of both male and female ground squirrels expressed torpor in the fall while still
housed conventionally and prior to cold exposure. The expression of torpor was not predicted by body weight or age, rather
it appears to be preprogrammed in a time-dependent manner that is independent of, yet enhanced by, environmental cues. The
timing and duration of these torpor bouts occurring prior to cold exposure were also remarkably sporadic. Thus, it is not
possible to know with certainty which animals are torpor-naive before cold exposure in the absence of continuous measurement
of body temperature. We conclude that fall animals encompass variable points in the transition between summer and winter phases
of the circannual cycle of hibernation, thereby confounding studies in which they are used as non-hibernating controls. Conversely,
these fall transition animals offer unique opportunities to define the molecular changes that accompany and enable hibernation. 相似文献
54.
L. Elaine Epperson James C. Rose Rae L. Russell Mrinalini P. Nikrad Hannah V. Carey Sandra L. Martin 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2010,180(4):599-617
During the torpor phase of mammalian hibernation when core body temperature is near 4°C, the autonomic system continues to
maintain respiration, blood pressure and heartbeat despite drastic reductions in brain activity. In addition, the hibernator’s
neuronal tissues enter into a protected state in which the potential for ischemia–reperfusion injury is markedly minimized.
Evolutionary adaptations for continued function and neuroprotection throughout cycles of torpor and euthermia in winter are
predicted to manifest themselves partly in changes in the brainstem proteome. Here, we compare the soluble brainstem protein
complement from six summer active ground squirrels and six in the early torpor (ET) phase of hibernation. Thirteen percent
of the ~1,500 quantifiable 2D gel spots alter significantly from summer to ET; the proteins identified in these differing
spots are known to play roles in energy homeostasis via the tricarboxylic acid cycle (8 proteins), cytoarchitecture and cell
motility (14 proteins), anabolic protein processes (13 proteins), redox control (11 proteins) and numerous other categories
including protein catabolism, oxidative phosphorylation, signal transduction, glycolysis, intracellular protein trafficking
and antiapoptotic function. These protein changes represent, at least in part, the molecular bases for restructuring of cells
in the brainstem, a shift away from glucose as the primary fuel source for brain in the winter, and the generation of a streamlined
mechanism capable of efficient and rapid energy production and utilization during the torpor and arousal cycles of hibernation. 相似文献
55.
GM1 binding-deficient exotoxin is a potent noninflammatory broad spectrum intradermal immunoadjuvant 总被引:2,自引:0,他引:2
Zoeteweij JP Epperson DE Porter JD Zhang CX Frolova OY Constantinides AP Fuhrmann SR El-Amine M Tian JH Ellingsworth LR Glenn GM 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(2):1197-1207
Intradermal (i.d.) immunization is a promising route of vaccine administration. Suitable i.d. adjuvants are important to increase vaccine efficacy in poorly responding populations such as the elderly or for dose-sparing strategies in the face of vaccine shortages. Bacterial exotoxins, such as Escherichia coli heat-labile enterotoxin (LT), exert strong immunostimulatory effects through binding to monosialoganglioside (GM1) cell surface receptors; however, injection is hampered by local inflammation. We demonstrate that the injection of LT formulations deficient in GM1 binding by mutation (LT(G33D)) or in vitro ligand coupling does not cause localized edema and inflammation in mice, yet these formulations retain potent adjuvant activity by enhancing functional Ab and cellular immune responses to coadministered Ags. Complete protection against in vivo lethal tetanus toxin challenge and the induction of Ag-specific CTL responses capable of killing target cells in vivo indicated in vivo efficacy of the induced immune responses. LT(G33D) proved superior to standard alum adjuvant regarding the magnitude and breadth of the induced immune responses. Immunizations in complex ganglioside knockout mice revealed a GM1-independent pathway of LT adjuvanticity. Immunostimulation by i.d. LT(G33D) is explained by its ability to induce migration of activated APCs to the proximal draining lymph nodes. LT(G33D) is a promising candidate adjuvant for human trials of parenteral vaccines in general and for current i.d. vaccine development in particular. 相似文献
56.
57.
Martin SL Epperson LE Rose JC Kurtz CC Ané C Carey HV 《American journal of physiology. Regulatory, integrative and comparative physiology》2008,295(1):R316-R328
The intestine of hibernating ground squirrels is protected against damage by ischemia-reperfusion (I/R) injury. This resistance does not depend on the low body temperature of torpor; rather, it is exhibited during natural interbout arousals that periodically return hibernating animals to euthermia. Here we use fluorescence two-dimensional difference gel electrophoresis (DIGE) to identify protein spot differences in intestines of 13-lined ground squirrels in the sensitive and protected phases of the circannual hibernation cycle, comparing sham-treated control animals with those exposed to I/R. Protein spot differences distinguished the sham-treated summer and hibernating samples, as well as the response to I/R between summer and hibernating intestines. The majority of protein changes among these groups were attributed to a seasonal difference between summer and winter hibernators. Many of the protein spots that differed were unambiguously identified by high-pressure liquid chromatography followed by tandem mass spectrometry of their constituent peptides. Western blot analysis confirmed significant upregulation for three of the proteins, albumin, apolipoprotein A-I, and ubiquitin hydrolase L1, that were identified in the DIGE analysis as increased in sham-treated hibernating squirrels compared with sham-treated summer squirrels. This study identifies several candidate proteins that may contribute to hibernation-induced protection of the gut during natural torpor-arousal cycles and experimental I/R injury. It also reveals the importance of enterocyte maturation in defining the hibernating gut proteome and the role of changing cell populations for the differences between sham and I/R-treated summer animals. 相似文献
58.
Epperson JR Deskus JA Gentile AJ Iben LG Ryan E Sarbin NS 《Bioorganic & medicinal chemistry letters》2004,14(4):1023-1026
A series of 4-substituted anilides with human melatonergic affinity is reported. Butyramides 26, 39, 42, 52, 57, and 58 all demonstrated subnanomolar MT(2) binding affinity and MT(2) selectivity of at least 70-fold over the MT(1) receptor. Compound 26 demonstrated full agonism at the MT(2) receptor. 相似文献
59.
Bacitracin is a widely used metal-dependent peptide antibiotic produced by Bacillus subtilis and Bacillus licheniformis with a potent bactericidal activity directed primarily against Gram-positive organisms. This antibiotic requires a divalent metal ion such as Zn(II) for its biological activity, and has been reported to bind several other transition metal ions, including Co(II), Ni(II), and Cu(II). Despite the wide use of bacitracin, a structure-activity relationship for this drug has not been established, and the structure of its metal complexes has not been fully determined. We report here one- and two-dimensional nuclear magnetic resonance (NMR) studies of the structure of the metal complexes of several bacitracin analogues by the use of paramagnetic Co(II) as a probe. The Co(II) complex of this antibiotic exhibits many well-resolved isotropically shifted (1)H NMR signals in a large spectral window ( approximately 200 ppm) due to protons near the metal, resulting from both contact and dipolar shift mechanisms. The assignment of the isotropically shifted (1)H NMR features concludes that bacitracin A(1), the most potent component of the bacitracin mixture, binds to Co(II) via the His-10 imidazole ring N(epsilon), the thiazoline nitrogen, and the monodentate Glu-4 carboxylate to form a labile complex in aqueous solutions. The free amine of Ile-1 does not bind Co(II). Several different analogues of bacitracin have also been isolated or prepared, and the studies of their Co(II) binding properties further indicate that the antimicrobial activity of these derivatives correlates directly to their metal binding mode. For example, the isotropically shifted (1)H NMR spectral features of the high-potent bacitracin analogues, including bacitracins A(1), B(1), and B(2), are virtually identical. However, Glu-4 and/or the thiazoline ring does not bind Co(II) in the bacitracin analogues with low antibiotic activities, including bacitracins A(2) and F. 相似文献
60.