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111.
Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) has been applied primarily to the analysis of glycosphingolipids separated from other complex mixtures by TLC, but it is difficult to obtain quantitative profiling of each glycosphingolipid among the different spots on TLC by MALDI-MS. Thus, the development of a convenient approach that utilizes liquid chromatography/electrospray ionization (LC/ESI)-MS has received interest. However, previously reported methods have been insufficient to separate and distinguish each ganglioside class. Here we report an effective method for the targeted analysis of theoretically expected ganglioside molecular species by LC/ESI tandem mass spectrometry (LC/ESI-MS/MS) in combination with multiple reaction monitoring (MRM). MRM detection specific for sialic acid enabled us to analyze ganglioside standards such as GM1, GM2, GM3, GD1, and GT1 at picomolar to femtomolar levels. Furthermore, other gangliosides, such as GD2, GD3, GT2, GT3, and GQ1, were also detected in glycosphingolipid standard mixtures from porcine brain and acidic glycolipid extract from mouse brain by theoretically expanded MRM. We found that this approach was also applicable to sulfatides contained in the glycosphingolipid mixtures. In addition, we established a method to separate and distinguish regioisomeric gangliosides, such as GM1a and -1b, GD1a, -1b, and -1c, and GT1a, -1b, and -1c with diagnostic sugar chains in the MRM. 相似文献
112.
Most of inherited retinal diseases such as retinitis pigmentosa (RP) cause photoreceptor cell death resulting in blindness. RP is a large family of diseases in which the photoreceptor cell death can be caused by a number of pathways. Among them, light exposure has been reported to induce photoreceptor cell death. However, the detailed mechanism by which photoreceptor cell death is caused by light exposure is unclear. In this study, we have shown that even a mild light exposure can induce ectopic phototransduction and result in the acceleration of rod photoreceptor cell death in some vertebrate models. In ovl, a zebrafish model of outer segment deficiency, photoreceptor cell death is associated with light exposure. The ovl larvae show ectopic accumulation of rhodopsin and knockdown of ectopic rhodopsin and transducin rescue rod photoreceptor cell death. However, knockdown of phosphodiesterase, the enzyme that mediates the next step of phototransduction, does not. So, ectopic phototransduction activated by light exposure, which leads to rod photoreceptor cell death, is through the action of transducin. Furthermore, we have demonstrated that forced activation of adenylyl cyclase in the inner segment leads to rod photoreceptor cell death. For further confirmation, we have also generated a transgenic fish which possesses a human rhodopsin mutation, Q344X. This fish and rd10 model mice show photoreceptor cell death caused by adenylyl cyclase. In short, our study indicates that in some RP, adenylyl cyclase is involved in photoreceptor cell death pathway; its inhibition is potentially a logical approach for a novel RP therapy. 相似文献
113.
Ikeda H Hirano Y Ziegler TA Saigusa M 《Journal of experimental zoology. Part A, Comparative experimental biology》2006,305(6):459-471
Hatching of embryos in the estuarine crab Sesarma haematocheir is highly synchronized with nocturnal high tide and completes within 1 hr among all embryos incubated by the female. This highly synchronized hatching is induced by a "Hatching-Program Inducing Factor (HPIF)" released from the female. To further define the cues involved in synchronized hatching, experiments were designed to characterize this factor and to determine possible sites of release and temporal release patterns using strategies involving isolation of egg masses, perfusion, and ablation experiments on fully developed embryos that had not yet entered the hatching program. Embryo transplantations indicate that not only HPIF may be released from the branchial chamber, but that it is extraordinarily unstable, and loses activity within 15 min, which frustrates further attempts at characterization. Nevertheless, with regard to temporal release patterns, it was established that HPIF activity was detected during short periods over three consecutive nights prior to release of larvae. This activity did not explain the gated response of embryo release in this crab, which might correspond with circatidal larval release events in the field. 相似文献
114.
We investigated the ability of Enteromorpha intestinalis (L.) Link to take up pulses of different species of nitrogen simultaneously, as this would be an important mechanism to enhance bloom ability in estuaries. Uptake rates and preference for NH4+ or NO3− following 1, 3, 6, 9, 12 or 24 h of exposure to either 15NH4NO3 or NH415NO3 were determined by disappearance of N from the medium. Differences in assimilation rates for NH4+ or NO3− were quantified by the accumulation of NH4+, NO3−, and atom % 15N in the algal tissue. NH4+ concentration was reduced more quickly than water NO3− concentration. Water column NH4+ concentration after the longest time interval was reduced from 300 to 50 μM. Water NO3− was reduced from 300 to 150 μM. The presence of 15N or 14N had no effect on uptake of either NH4+ or NO3−. 15N was removed from the water at an almost identical rate and magnitude as 14N. Differences in accumulation of 15NH4+ and 15NO3− in the tissue reflected disappearance from the water; 15N from NH4+ accumulated faster and reached an atom % twice that of 15N from NO3−. This outcome suggested that when NH4+ and NO3− were supplied in equal concentrations, more NH4+ was taken up and assimilated. The ability to take up high concentrations of NH4+, and NO3− simultaneously is important for bloom-forming species of estuarine macroalgae subject to multiple nutrient species from various sources. 相似文献
115.
116.
Toshiaki Miyazaki Kazuhiro Ikeda Kuniko Horie-Inoue Satoshi Inoue 《Biochemical and biophysical research communications》2014
Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer’s disease. We previously showed that APP is a primary androgen-responsive gene in prostate cancer and that its increased expression is correlated with poor prognosis for patients with prostate cancer. APP has also been implicated in several human malignancies. Nevertheless, the mechanism underlying the pro-proliferative effects of APP on cancers is still not well-understood. In the present study, we explored a pathophysiological role for APP in prostate cancer cells using siRNA targeting APP (siAPP). The proliferation and migration of LNCaP and DU145 prostate cancer cells were significantly suppressed by siAPP. Differentially expressed genes in siAPP-treated cells compared to control siRNA-treated cells were identified by microarray analysis. Notably, several metalloproteinase genes, such as ADAM10 and ADAM17, and epithelial–mesenchymal transition (EMT)-related genes, such as VIM, and SNAI2, were downregulated in siAPP-treated cells as compared to control cells. The expression of these genes was upregulated in LNCaP cells stably expressing APP when compared with control cells. APP-overexpressing LNCaP cells exhibited enhanced migration in comparison to control cells. These results suggest that APP may contribute to the proliferation and migration of prostate cancer cells by modulating the expression of metalloproteinase and EMT-related genes. 相似文献
117.
118.
Role of follicular dendritic cells in the early HIV-1 infection: in vitro model without specific antibody 总被引:2,自引:0,他引:2
Taruishi M Terashima K Dewan Z Yamamoto N Ikeda S Kobayashi D Eishi Y Yamazaki M Furusaka T Sugimoto M Ishii M Kitamura K Yamamoto N 《Microbiology and immunology》2004,48(9):693-702
About 90% of HIV-1 RNA in the lymph nodes is reported to localize in follicular dendritic cellsnetwork (FDC-NW) as early as several days after infection and as much as that in the late stage. But the mechanism remains to be fully understood. To elucidate the role of follicular dendritic cells (FDC) in the early stage of HIV-1 infection, FDC-like cell strains (FDCLC) were established and they were characterized in the co-culture system with T cells for their effect on HIV-1 trapping and replication in p24 immunoassay, immunohistochemistry as well as confocal and electronmicroscopy. Established FDCLC were positive for CNA-42, S-100alpha and intercellular desmosome-like junctions. L-SIGN and DC-SIGN were also detected in FDCLC. Alu-HIV-1 PCR analysis showed no HIV-1 integration in FDCLC. FDCLC trapped HIV-1 and transferred them to uninfected MOLT-4 T cells (MOLT-4) efficiently in the absence of specific antibody. FDCLC also accelerated HIV-1 replication in HIV-1-pre-exposed MOLT-4. These unique FDCLC effects were explained, at least partly, by the fact that FDCLC up-regulated CD4 expression in MOLT-4 and helped T cells escape from apoptosis in the co-culture. These data suggest that FDC/FDCLC engage not only in trapping but also in active expansion of HIV-1 in the absence of specific antibody. 相似文献
119.
Ikeda T Yaegashi T Matsuzaki T Yamazaki R Hashimoto S Sawada S 《Bioorganic & medicinal chemistry letters》2011,21(19):5978-5981
We previously reported that phenanthroindolizidine alkaloid 3 and its derivatives had markedly potent in vitro cytotoxicity. However, they had low in vivo antitumor activities and high in vivo toxicities, which was a serious problem. To address this problem, new phenanthroindolizidine derivatives were synthesized and their antitumor activities and toxicities were evaluated. This study describes the relationship between the chemical structures, antitumor activities, and toxicities of these phenanthroindolizidine derivatives. Based on its properties, compound 8 was found to be the most suitable potential antitumor agent. 相似文献
120.
The B subunit of cholera toxin enhances DNA synthesis in rat hepatocytes induced by insulin and epidermal growth factor. 总被引:2,自引:0,他引:2
H Mitsui M Iwamori N Hashimoto H Yamada Y Ikeda G Toda K Kurokawa Y Nagai 《Biochemical and biophysical research communications》1991,174(1):372-378
The B subunit of cholera toxin, which binds to ganglioside GM1, enhanced DNA synthesis in rat hepatocytes in primary culture induced by insulin and/or epidermal growth factor. The effect was dose-dependent, and whole cholera toxin, activating adenylate cyclase, showed a higher effect than the B subunit alone. The B subunit acted additively with other agents that also increase cyclic AMP levels. A competitive antagonist of cyclic AMP could not suppress the effect of the B subunit completely. These data suggest that the effect is independent of the cyclic AMP signal pathway, and that GM1 plays a role in hepatocyte proliferation. 相似文献