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11.
Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells 总被引:3,自引:0,他引:3
Substrate regulation of System A transport activity in rat H4 hepatoma cells is described. The uptake of several amino acids was tested in the presence of system-specific inhibitors. System A activity was increased in a RNA- and protein synthesis-dependent manner by amino acid deprivation of the cells (adaptive regulation), whereas transport by Systems ASC, N, y+, and L was unaffected. Unlike human fibroblasts, the H4 cells did not require serum to exhibit the depression of System A. At cell densities between 88 X 10(3) and 180 X 10(3) cells/cm2, the degree of adaptive regulation was inversely related to cell density. Both transport of AIB and adaptive regulation of System A were nearly abolished if either K+ or Li+ was substituted for Na+ in the medium. The presence of cycloheximide or tunicamycin blocked further increases in starvation-induced activity within 1 hr of addition, suggesting the involvement of a plasma membrane glycoprotein. In contrast, if the medium was supplemented with actinomycin after the stimulation of System A had begun, the activity continued to increase for an additional 2 hr before being slowed by the inhibitor. The contributions of trans-inhibition and repression to the amino acid-induced decay of System A activity were estimated for several representative amino acids. In general, the System A activity in normal rat hepatocytes was much less sensitive to trans-inhibition than the corresponding activity in H4 hepatoma cells. The half-life values for the amino acid-dependent decay of System A ranged from 0.5 to 2.0 hr. 相似文献
12.
Seed Dormancy in Red Rice : VII. Structure-Activity Studies of Germination Stimulants 总被引:1,自引:0,他引:1 下载免费PDF全文
Many chemically dissimilar substances break dormancy of seeds, but the relationship between chemical structure and physiological activity is unknown. In this study, the concentrations of organic acids, esters, aldehydes, alcohols, and inorganic weak acids required to elicit 50% germination of initially dormant, dehulled red rice seeds (Oryza sativa) were determined. The activity of most substances was very highly and inversely correlated to lipophilicity as measured by octanol/water partition coefficients; chemicals with the highest partition coefficients required the lowest concentrations to elicit the germination response. Relative efficacy was also dependent upon the functional group; generally, monocarboxylic acids were more effective than aldehydes, esters, hydroxyacids, and alcohols. Relative hydrophobicity plots supported a modulating role of the functional group. Dormancy-breaking activity of methyl formate, formic acid, nitrite, azide, and cyanide was higher than predicted based on lipophilicity and apparently was related to molecular size; compounds with smaller molecular widths were required at lower concentrations to achieve the 50% germination response. 相似文献
13.
Background
Predicting drug-protein interactions from heterogeneous biological data sources is a key step for in silico drug discovery. The difficulty of this prediction task lies in the rarity of known drug-protein interactions and myriad unknown interactions to be predicted. To meet this challenge, a manifold regularization semi-supervised learning method is presented to tackle this issue by using labeled and unlabeled information which often generates better results than using the labeled data alone. Furthermore, our semi-supervised learning method integrates known drug-protein interaction network information as well as chemical structure and genomic sequence data.Results
Using the proposed method, we predicted certain drug-protein interactions on the enzyme, ion channel, GPCRs, and nuclear receptor data sets. Some of them are confirmed by the latest publicly available drug targets databases such as KEGG.Conclusions
We report encouraging results of using our method for drug-protein interaction network reconstruction which may shed light on the molecular interaction inference and new uses of marketed drugs.14.
Blois JT Mataraza JM Mecklenbraüker I Tarakhovsky A Chiles TC 《The Journal of biological chemistry》2004,279(29):30123-30132
The cAMP-response element-binding protein (CREB) is activated by phosphorylation on Ser-133 and plays a key role in the proliferative and survival responses of mature B cells to B cell receptor (BCR) signaling. The signal link between the BCR and CREB activation depends on a phorbol ester (phorbol 12-myristate 13-acetate)-sensitive protein kinase C (PKC) activity and not protein kinase A or calmodulin kinase; however, the identity and role of the PKC(s) activity has not been elucidated. We found the novel PKCdelta (nPKCdelta) activator bistratene A is sufficient to induce CREB phosphorylation in murine splenic B cells. The pharmacological inhibitor G?6976, which targets conventional PKCs and PKCmu, has no effect on CREB phosphorylation, whereas the nPKCdelta inhibitor rottlerin blocks CREB phosphorylation following BCR cross-linking. Bryostatin 1 selectively prevents nPKCdelta depletion by phorbol 12-myristate 13-acetate when coapplied, coincident with protection of BCR-induced CREB phosphorylation. Ectopic expression of a kinase-inactive nPKCdelta blocks BCR-induced CREB phosphorylation in A20 B cells. In addition, BCR-induced CREB phosphorylation is significantly diminished in nPKCdelta-deficient splenic B cells in comparison with wild type mice. Consistent with the essential role for Bruton's tyrosine kinase and phospholipase Cgamma2 in mediating PKC activation, Bruton's tyrosine kinase- and phospholipase Cgamma2-deficient B cells display defective CREB phosphorylation by the BCR. We also found that p90 RSK directly phosphorylates CREB on Ser-133 following BCR cross-linking and is positioned downstream of nPKCdelta. Taken together, these results suggest a model in which BCR engagement leads to the phosphorylation of CREB via a signaling pathway that requires nPKCdelta and p90 RSK in mature B cells. 相似文献
15.
Morris TA Marsh JJ Chiles PG Pedersen CA Konopka RG Gamst AC Loza O 《American journal of physiology. Heart and circulatory physiology》2004,287(2):H818-H822
The role of active thrombosis in the pathophysiology of pulmonary embolism is unclear. We tested the hypothesis that venous thrombi significantly increase their thrombotic activity once they embolize into the high-flow circulation of the pulmonary arteries. Thrombotic activity was measured using an immunoassay that measures both fibrinopeptide B (FPB) as well as its most abundant metabolite des-arginine FPB. Thrombi were formed in the femoral veins of adult dogs. In one group, the thrombi were embolized without anticoagulation. In the second group, heparin (300 U/kg bolus, then 90 U x kg(-1) x h(-1) infusion) was administered before embolization to prevent subsequent thrombotic activity. Plasma FPB concentrations were significantly suppressed in the heparinized group relative to the nonheparinized group for 1 h postembolization (P = 0.038). We conclude that pulmonary embolization itself causes preexisting venous thrombi to greatly intensify their thrombotic activity and that embolization-associated thrombus propagation can be prevented by heparin. 相似文献
16.
Requirement for a hsp90 chaperone-dependent MEK1/2-ERK pathway for B cell antigen receptor-induced cyclin D2 expression in mature B lymphocytes 总被引:7,自引:0,他引:7
A requirement for cyclin D2 in G(1)-to-S phase progression has been definitively established in mature B cells stimulated via the B cell antigen receptor (BCR). However, the identity of constituents of the BCR signaling cascade that leads to cyclin D2 accumulation remains incomplete. We report that inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-1/2 blocked BCR-induced activation of extracellular signal-regulated kinase (ERK). Inhibition of the MEK1/2-ERK pathway was sufficient to abrogate BCR-induced cyclin D2 expression at the mRNA and protein levels. Disruption of endogenous heat shock protein 90 (hsp90) function with geldanamycin abrogated BCR-induced cyclin D2 expression and proliferation. Geldanamycin effects were attributed to a selective depletion of cellular Raf-1 that interrupted BCR-coupled activation of MEK1/2 and ERK. By contrast, signaling through the phosphatidylinositol 3-kinase and protein kinase C pathways was not affected, suggesting that disruption of hsp90 function did not cause a general impairment of BCR signaling. These results suggest that the MEK1/2-ERK pathway is essential for BCR signaling to cyclin D2 accumulation in ex vivo splenic B lymphocytes. Furthermore, these findings imply that hsp90 function is required for BCR signaling through the Raf-1-MEK1/2-ERK pathway but not through the phosphatidylinositol 3-kinase- or protein kinase C-dependent pathways. 相似文献
17.
K. T. Bird T. C. Chiles R. E. Longley A. F. Kendrick M. D. Kinkema 《Journal of applied phycology》1993,5(2):213-218
Protein extracts from 22 species of marine macroalgae from Florida and North Carolina were compared for their abilities to
agglutinate sheep and rabbit erythrocytes. Protein extracts from 21 algal species agglutinated rabbit erythrocytes compared
to 19 for sheep erythrocytes. However, agglutination by brown algal extracts was variable. The agglutination produced by protein
extracts from Dictyota dichotoma could be blocked by addition of polyvinylpyrrolidone. Protein extracts from North Carolina macroalgae were also tested against
five bacterial species. Three of these agglutinated bacterial cells. Ulva curvata and Bryopsis plumosa agglutinated all five species. Protein extracts from five species of Florida algae were tested for their effects on mitogenesis
in mouse splenocytes and human lymphocytes. Gracilaria tikvahiae HBOI Strain G-5, Ulva rigida and Gracilaria verrucosa HBOI Strain G-16S stimulated mitogenesis in mouse splenocytes, while Gracilaria tikvahiae HBOI Strain G-16stimulated mitogenesis in human lymphocytes. 相似文献
18.
Chiles TC 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(5):2901-2907
Abs produced by B lymphocytes play an essential role in humoral immunity against pathogens. This response is dependent upon the extent of genome replication, which in turn allows clonal expansion of Ag-specific B cell precursors. Thus, there is considerable interest in understanding how naive B cells commit to genome replication following Ag challenge. The BCR is a key regulator of B cell growth responses in the bone marrow and the periphery. The importance of identifying BCR-coupled signaling networks and their cell cycle targets is underscored by the recognition that aberrant cell cycle control can lead to lymphoproliferative disorders or lymphoid malignancies. This review focuses on recent progress toward understanding the function of cyclin D2 in cell cycle control, and in the development of murine B lymphocytes. 相似文献
19.
20.
Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. (3)H-SR48692 bound with high affinity (IC(50) = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific (125)I-NT binding with high affinity (IC(50) values of 2 and 200 nM). In contrast, the NT(2) receptor agonist, levocabastine, had little effect on specific (125)I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 microM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 microM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT(1) receptor antagonist which inhibits SCLC growth. 相似文献