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61.
In proteobacteria, genes whose expression is modulated in response to the external concentration of inorganic phosphate are often regulated by the PhoB protein which binds to a conserved motif (Pho box) within their promoter regions. Using a position weight matrix algorithm derived from known Pho box sequences, we identified 96 putative Pho regulon members whose promoter regions contained one or more Pho boxs in the Sinorhizobium meliloti genome. Expression of these genes was examined through assays of reporter gene fusions and through comparison with published microarray data. Of 96 genes, 31 were induced and 3 were repressed by Pi starvation in a PhoB dependent manner. Novel Pho regulon members included several genes of unknown function. Comparative analysis across 12 proteobacterial genomes revealed highly conserved Pho regulon members including genes involved in Pi metabolism (pstS, phnC and ppdK). Genes with no obvious association with Pi metabolism were predicted to be Pho regulon members in S.meliloti and multiple organisms. These included smc01605 and smc04317 which are annotated as substrate binding proteins of iron transporters and katA encoding catalase. This data suggests that the Pho regulon overlaps and interacts with several other control circuits, such as the oxidative stress response and iron homeostasis. 相似文献
62.
Meng JP Ceryak S Aratsu Z Jones L Epstein L Bouscarel B 《American journal of physiology. Cell physiology》2006,291(3):C546-C554
We have previously reported that the bile acids chenodeoxycholate (CDCA) and ursodeoxycholate (UDCA) decreased PGE1-induced cAMP production in a time- and dose-dependent manner not only in hepatocytes but also in nonhepatic cells, including dermal fibroblasts. In the present study, we investigated the physiological relevance of this cAMP modulatory action of bile acids. PGE1 induced cAMP production in a time- and dose-dependent manner. Moreover, PGE1 (1 µM), forskolin (110 µM), and the membrane-permeable cAMP analog CPT-cAMP (0.110 µM) decreased dermal fibroblast proliferation in a dose-dependent manner with a maximum inhibition of 80%. CDCA alone had no significant effect on cell proliferation at a concentration up to 25 µM. However, CDCA significantly reduced PGE1-induced cAMP production by 8090% with an EC50 of 20 µM. Furthermore, at concentrations 25 µM, CDCA significantly attenuated the PGE-1-induced decreased cell proliferation. However, at concentrations of 50 µM and above, while still able to almost completely inhibit PGE-1-induced cAMP production, CDCA, at least in part through an increased cyclooxygenase-2 (COX-2) expression level and PGE2 synthesis, produced a direct and significant decrease in cell proliferation. Indeed, the CDCA effect was partially blocked by 5070% by both indomethacin and dexamethasone. In addition, overexpression of COX-2 cDNA wild type resulted in an increased efficacy of CDCA to block cell proliferation. The effects of CDCA on both cAMP production and cell proliferation were similar to those of UDCA and under the same conditions cholate had no effect. Results of the present study underline pathophysiological consequences of cholestatic hepatobiliary disorders, in which cells outside of the enterohepatic circulation can be exposed to elevated bile acid concentrations. Under these conditions, low bile acid concentrations can attenuate the negative hormonal control on cell proliferation, resulting in the stimulation of cell growth, while at high concentrations these bile acids provide for a profound and prolonged inhibition of cell proliferation. chenodeoxycholic acid; cyclic adenosine monophosphate 相似文献
63.
A set of TROSY-HNCO (tHNCO)-based 3D experiments is presented for measuring 15N relaxation parameters in large, membrane-associated proteins, characterized by slow tumbling times and significant spectral
overlap. Measurement of backbone 15N R
1, R
1ρ, 15N–{1H} NOE, and 15N CSA/dipolar cross correlation is demonstrated and applied to study the dynamic behavior of the homotetrameric KcsA potassium
channel in SDS micelles under conditions where this channel is in the closed state. The micelle-encapsulated transmembrane
domain, KcsATM, exhibits a high degree of order, tumbling as an oblate ellipsoid with a global rotational correlation time, τc = 38 ± 2.5 ns, at 50 °C and a diffusion anisotropy, , corresponding to an aspect ratio a/b ≥ 1.4. The N- and C-terminal intracellular segments of KcsA exhibit considerable internal dynamics (S
2 values in the 0.2–0.45 range), but are distinctly more ordered than what has been observed for unstructured random coils.
Relaxation behavior in these domains confirms the position of the C-terminal helix, and indicates that in SDS micelles, this
amphiphilic helix does not associate into a stable homotetrameric helical bundle. The relaxation data indicate the absence
of elevated backbone dynamics on the ps–ns time scale for the 5-residue selectivity filter, which selects K+ ions to enter the channel.
Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .
An erratum to this article can be found at 相似文献
64.
Zaheer Ul-Haq Waqasuddin Khan Saima Kalsoom Farzana L Ansari 《Theoretical biology & medical modelling》2010,7(1):22
Background
Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques. 相似文献65.
Acetylcholine is the major excitatory neurotransmitter in the central nervous system of insects. Mutant analysis of the Dα7 nicotinic acetylcholine receptor (nAChR) ofDrosophila shows that it is required for the giant fiber-mediated escape behavior. The Dα7 protein is enriched in the dendrites of the giant fiber, and electrophysiological analysis of the giant fiber circuit showed that sensory input to the giant fiber is disrupted, as is transmission at an identified cholinergic synapse between the peripherally synapsing interneuron and the dorsal lateral muscle motor neuron. Moreover, we found thatgfA1, a mutation identified in a screen for giant fiber defects more than twenty years ago, is an allele ofDα7. Therefore, a combination of behavioral, electrophysiological, anatomical, and genetic data indicate an essential role for the Dα7 nAChR in giant fiber-mediated escape inDrosophila. 相似文献
66.
A constant-time, Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation, R(2), dispersion experiment for carbonyl carbons was designed and executed to detect micros-ms time-scale dynamics of protein backbone carbonyl sites. Because of the large (ca. 55 Hz) C(alpha)-C' J-coupling, the carbonyl signal intensity is strongly modulated as the spacing between CPMG pulses is varied, in uniformly (13)C enriched proteins, unless care is taken to minimize the perturbation of the C(alpha) magnetization by the CPMG pulses. CPMG pulse trains consisting of either a band-selective pulse, such as RE-BURP, or rectangular (with an excitation null in the C(alpha) region of the spectrum) pulses were employed in order to minimize C' signal modulation by C(alpha)-C' J-coupling. The performance of these types of CPMG refocusing pulses was assessed by computer simulation, and by comparing dispersion profiles measured for (1) uniformly [(13)C,(15)N, (2)H] ((2)H at non-labile hydrogen sites) labeled, and (2) uniformly (15)N/selectively-(13)C' labeled samples of HIV-1 protease bound to a potent inhibitor, DMP323. In addition, because the uniformly (13)C/(15)N/(2)H labeled sample was well suited to measure (15)N and (1)H R(2) dispersion as well as (13)C' dispersion, conformational exchange in the inter subunit beta-sheet hydrogen-bond network of the inhibitor-bound protease was elucidated using relaxation dispersion data of all three types of nuclei. 相似文献
67.
68.
Lim Ramon Zaheer Asgar Kraakevik Jeff A. Darby Christine J. Oberley Larry W. 《Neurochemical research》1998,23(11):1445-1451
In order to evaluate the intracellular function of glia maturation factor (GMF), we overexpressed GMF in C6 rat glioma cells using two methods: stable transfection using the pcDNA3 plasmid, and transient transfection using replication-defective human adenovirus. With both methods, C6 cells transfected with GMF and overexpressing the protein exhibit a lower saturation density in culture compared to non-transfected or vector alone controls. Transfected cells also exhibit morphological differentiation as shown by the outgrowth of cell processes. When inoculated into nude mice, transfected cells are less tumorigenic than controls, and express the mature astrocytic marker glial fibrillary acidic protein. In tissue culture, transfected cells show a 3.5-fold increase in CuZn-dependent superoxide dismutase (CuZnSOD) activity. Western blot analysis reveals a 3.5-fold increase in CuZnSOD protein, suggesting an induction of the enzyme. In view of recent findings that reactive oxygen species (ROS) and the antioxidant enzymes are intricately involved in key physiologic processes such as proliferation, differentiation and apoptosis, the study raises the possibility that CuZnSOD may be a mediator of GMF function. 相似文献
69.
Milena Sochor Najma Zaheer Baquer John S. Hothersall Patricia McLean 《Biochemical and biophysical research communications》1978,80(3):533-539
Measurements have been made of the activity of ornithine decarboxylase of liver, heart, kidney and brain in alloxan-diabetic and control rats. In all these tissues this enzyme had decreased markedly at four weeks after induction of diabetes. These results are discussed in relation to the hormonal control and cyclic nucleotide regulation of ornithine decarboxylase. 相似文献
70.
Alrefai WA Sarwar Z Tyagi S Saksena S Dudeja PK Gill RK 《American journal of physiology. Gastrointestinal and liver physiology》2005,288(5):G978-G985
Bile acids are efficiently absorbed from the intestinal lumen via the ileal apical sodium-dependent bile acid transporter (ASBT). ASBT function is essential for maintenance of cholesterol homeostasis in the body. The molecular mechanisms of the direct effect of cholesterol on human ASBT function and expression are not entirely understood. The present studies were undertaken to establish a suitable in vitro experimental model to study human ASBT function and its regulation by cholesterol. Luminal membrane bile acid transport was evaluated by the measurement of sodium-dependent 3H-labeled taurocholic acid (3H-TC) uptake in human intestinal Caco-2 cell monolayers. The relative abundance of human ASBT (hASBT) mRNA was determined by real-time PCR. Transient transfection and luciferase assay techniques were employed to assess hASBT promoter activity. Caco-2 cell line was found to represent a suitable model to study hASBT function and regulation. 25-Hydroxycholesterol (25-HCH; 2.5 microg/ml for 24 h) significantly inhibited Na(+)-dependent 3H-TC uptake in Caco-2 cells. This inhibition was associated with a 50% decrease in the V(max) of the transporter with no significant changes in the apparent K(m). The inhibition in hASBT activity was associated with reduction in both the level of hASBT mRNA and its promoter activity. Our data show the inhibition of hASBT function and expression by 25-HCH in Caco-2 cells. These data provide novel evidence for the direct regulation of human ASBT function by cholesterol and suggest that this phenomenon may play a central role in cholesterol homeostasis. 相似文献