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91.
Misra UK Gonzalez-Gronow M Gawdi G Hart JP Johnson CE Pizzo SV 《The Journal of biological chemistry》2002,277(44):42082-42087
The low density lipoprotein receptor-related protein (LRP) is a scavenger receptor that binds to many proteins, some of which trigger signal transduction. Receptor-recognized forms of alpha(2)-Macroglobulin (alpha(2)M*) bind to LRP, but the pattern of signal transduction differs significantly from that observed with other LRP ligands. For example, neither Ni(2+) nor the receptor-associated protein, which blocks binding of all known ligands to LRP, block alpha(2)M*-induced signal transduction. In the current study, we employed alpha(2)-macroglobulin (alpha(2)M)-agarose column chromatography to purify cell surface membrane binding proteins from 1-LN human prostate cancer cells and murine macrophages. The predominant binding protein purified from 1-LN prostate cancer cells was Grp 78 with small amounts of LRP, a fact that is consistent with our previous observations that there is little LRP present on the surface of these cells. The ratio of LRP:Grp 78 is much higher in macrophages. Flow cytometry was employed to demonstrate the presence of Grp 78 on the cell surface of 1-LN cells. Purified Grp 78 binds to alpha(2)M* with high affinity (K(d) approximately 150 pm). A monoclonal antibody directed against Grp 78 both abolished alpha(2)M*-induced signal transduction and co-precipitated LRP. Ligand blotting with alpha(2)M* showed binding to both Grp 78 and LRP heavy chains in these preparations. Use of RNA interference to silence LRP expression had no effect on alpha(2)M*-mediated signaling. We conclude that Grp 78 is essential for alpha(2)M*-induced signal transduction and that a "co-receptor" relationship exists with LRP like that seen with several other ligands and receptors such as the uPA/uPAR (urinary type plasminogen activator or urokinase/uPA receptor) system. 相似文献
92.
Ligation of alpha(2)-macroglobulin receptors by receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*) activates various signaling cascades and promotes cell proliferation. It also elevates cAMP in murine peritoneal macrophages. We now report that a significant elevation of cAMP-response element-binding protein (CREB) occurs in alpha(2)M*-stimulated cells, and this effect is potentiated by isobutylmethylxanthine, dibutyryl-cAMP, or forskolin. An alpha(2)M* concentration-dependent rapid increase in phosphorylated CREB at Ser(133) also occurred, a necessary event in its activation. Inhibition of Ca(2+)/calmodulin kinase, protein kinases A and C, tyrosine kinases, ribosomal S6 kinase, farnesyl transferase, extracellular signal-regulated kinases 1/2, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase markedly reduce alpha(2)M*-induced phosphorylation of CREB, indicating a role for the p21(ras)-dependent and phosphatidylinositol 3-kinase signaling pathways in regulating CREB activation by alpha(2)M*. Finally, silencing the CREB gene by transfecting cells with a homologous gene sequence double-stranded RNA drastically reduced the expression of CREB and blocked the ability of alpha(2)M* to promote macrophage cell division. We conclude that cAMP-dependent signal transduction as well as other signaling cascades are essential for alpha(2)M*-induced cell proliferation. 相似文献
93.
94.
Stephanopoulos G Hwang D Schmitt WA Misra J Stephanopoulos G 《Bioinformatics (Oxford, England)》2002,18(8):1054-1063
MOTIVATION: The increasing use of DNA microarrays to probe cell physiology requires methods for visualizing different expression phenotypes and explicitly connecting individual genes to discriminating expression features. Such methods should be robust and maintain biological interpretability. RESULTS: We propose a method for the mapping of the physiological state of cells and tissues from multidimensional expression data such as those obtained with DNA microarrays. The method uses Fisher discriminant analysis to create a linear projection of gene expression measurements that maximizes the separation of different sample classes. Relative to other typical classification methods, this method provides insights into the discriminating characteristics of expression measurements in terms of the contribution of individual genes to the definition of distinct physiological states. This projection method also facilitates visualization of classification results in a reduced dimensional space. Examples from four different cases demonstrate the ability of the method to produce well-separated groups in the projection space and to identify important genes for defining physiological states. The method can be augmented to also include data from the proteomic and metabolic phenotypes and can be useful in disease diagnosis, drug screening and bioprocessing applications. 相似文献
95.
96.
Despite speculation that the muscarinic cholinergic antagonist, scopolamine, may influence the olfactory sensitivity of rats, there have been no definitive studies on this point to date. In this study, we examined the influence of a range of doses of scopolamine hydrobromine (namely, 0.10, 0.125, 0.15 and 0.20 mg/kg i.p.) on the odor detection performance of 15 adult male Long-Evans rats to ethyl acetate. Air-dilution olfactometry and a go/no-go operant signal detection task were employed. The drug conditions and a saline control were administered to each animal in an order counterbalanced by Latin squares, with 2 day intervals interspersed between tests. Scopolamine had no significant influence on odor detection performance per se, as measured by percent correct S+ and S- responses and a non-parametric signal detection measure of sensitivity. This is in contrast to the relatively large effects previously observed in the same test paradigm for such drugs as the D-1 agonist SKF 38393 and the D-2 agonist quinpirole. These data suggest that scopolamine has no meaningful influence on a well-practiced odor detection task. 相似文献
97.
Ghildiyal HC Misra T Keswani NK Agrahari D 《Plastic and reconstructive surgery》2003,112(4):1175-1176
98.
Pant HC Sharma RK Patel SH Shukla HR Mittal AK Kasiraj R Misra AK Prabhakar JH 《Theriogenology》2003,60(1):27-34
The objectives of this study were to determine the relationship of age and body weight to testicular development and to establish norms for breeding soundness evaluations of Murrah buffalo bulls. Testicular measurements of 133 Murrah buffalo bulls of various ages were recorded with a caliper and a tape. Semen was collected twice a week for 5 weeks from groups of bulls which were 25-36 (n=17), 37-48 (n=16), 49-60 (n=14), of >60 (n=10) months of age. After examining volume, sperm concentration, and progressive motility semen was diluted in Tris-citric acid-egg yolk-fructose extender and frozen in 0.5 ml French straws. Testicular measurements of buffalo bulls were lower than those recorded for European breeds of cattle bulls. Nevertheless, like cattle bulls, scrotal circumference was highly correlated with other testicular measurements. Also, it had a significant positive relationship with semen volume and sperm concentration per ejaculate. Average sperm output per week in order of increasing age group was 15.3, 18.2, 19.8 and 23.6 x 10(9). Corresponding values for sperm output per week per gram of testis were 59.1, 45.8, 41.1, 36.2 x 10(6) indicating a reduction in spermatogenesis per unit of testis with advancing age. Compared to European breeds, daily sperm output in Murrah bulls was nearly 45% lower, presumably due to their nearly 40% lower scrotal circumference than Holstein bulls of the same age. These results indicate that in buffalo, as in cattle, scrotal circumference is a useful indicator of potential sperm output and may serve as an important criterion for selecting young bulls as AI sires. 相似文献
99.
Complexes of four peptides [KWGK, KGWK, K(6MeW)GK, KG(6MeW)K] with the nucleic acids [poly(A), poly(C), poly(U), poly(I), and rG(8)] have been investigated by phosphorescence and optically detected magnetic resonance (ODMR) spectroscopy. The intrinsic spectroscopic probes used in these studies are tryptophan (W) and 6-methyltryptophan (6MeW). Binding to the nucleic acids results in a red-shift of the phosphorescence 0,0-band (delta E(0,0)) of the aromatic residue as well as a reduction of its zero-field splitting parameter (delta D). Results are compared with earlier studies of the HIV-1 nucleocapsid protein, NCp7, that contains a single tryptophan residue (Trp37) within a retroviral zinc finger sequence. Binding of poly(A) or poly(U) to the tetrapeptides induces larger delta E(0,0) and delta D than when bound to NCp7, indicating stronger stacking interactions. Poly(I), on the other hand, produces larger shifts in Trp37 of NCp7. Binding of rG(8) produces sequence-dependent effects in the peptides. When bound to NCp7, but in contrast with tetrapeptide binding, nucleic acids produce large changes in triplet state kinetics consistent with enhanced spin-orbit coupling. These results are discussed in terms of three limiting types of tryptophan-base interaction: intercalation, aromatic stacking, and edge-on interaction. These should have differing effects on the properties of the triplet state. 相似文献
100.
The endoplasmic reticulum (ER) molecular chaperone, BiP, plays a role in the cotranslational translocation and subsequent
folding and assembly of newly synthesized proteins targeted to the ER and secretory pathway. The sequence encoding a Douglas-fir
(Pseudotsuga menziesii [Mirb] Franco) BiP homologue (PmBiP) was identified by differential screening of a seedling cDNA library. Southern blotting
indicated that PmBiP is most likely present as a single copy. The deduced amino acid sequence of PmBiP contains an HEEL tetrapeptide
sequence which functions to retain PmBiP in the ER and is different from HDEL commonly found in angiosperm plant BiPs. Amino
acid sequence alignment and phylogenetic analysis show that PmBiP is highly similar to other plant BiPs yet forms a distinct
phylogenetic subgroup which is separate from the angiosperm BiPs. Northern and western blotting revealed that PmBiP is subject
to developmental regulation during seed development, germination, and early seedling growth and is seasonally regulated in
needles of young seedlings.
Received: 21 February 2000 / Accepted: 13 April 2000 相似文献