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51.
Nakata H Maeda K Miyakawa T Shibayama S Matsuo M Takaoka Y Ito M Koyanagi Y Mitsuya H 《Journal of virology》2005,79(4):2087-2096
We established human peripheral blood mononuclear cell (PBMC)-transplanted R5 human immunodeficiency virus type 1 isolate JR-FL (HIV-1(JR-FL))-infected, nonobese diabetic-SCID, interleukin 2 receptor gamma-chain-knocked-out (NOG) mice, in which massive and systemic HIV-1 infection occurred. The susceptibility of the implanted PBMC to the infectivity and cytopathic effect of R5 HIV-1 appeared to stem from hyperactivation of the PBMC, which rapidly proliferated and expressed high levels of CCR5. When a novel spirodiketopiperazine-containing CCR5 inhibitor, AK602/ONO4128/GW873140 (molecular weight, 614), was administered to the NOG mice 1 day after R5 HIV-1 inoculation, the replication and cytopathic effects of R5 HIV-1 were significantly suppressed. In saline-treated mice (n = 7), the mean human CD4(+)/CD8(+) cell ratio was 0.1 on day 16 after inoculation, while levels in mice (n = 8) administered AK602 had a mean value of 0.92, comparable to levels in uninfected mice (n = 7). The mean number of HIV-RNA copies in plasma in saline-treated mice were approximately 10(6)/ml on day 16, while levels in AK602-treated mice were 1.27 x 10(3)/ml (P = 0.001). AK602 also significantly suppressed the number of proviral DNA copies and serum p24 levels (P = 0.001). These data suggest that the present NOG mouse system should serve as a small-animal AIDS model and warrant that AK602 be further developed as a potential therapeutic for HIV-1 infection. 相似文献
52.
Takashi Nagata Mitsumasa Koyanagi Hisao Tsukamoto Akihisa Terakita 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(1):51-59
Peropsin, a member of the opsin family, has characteristics of two functionally distinct opsin-groups, that is, amino acid
residues conserved among opsins for light-sensing and a retinal-photoisomerase-like molecular property. Although such a bilateral
feature of peropsin seems to be important for understanding the diversity of the opsin family, previous studies have been
limited to higher deuterostome, vertebrate and amphioxus peropsins. Here, we report a protostome peropsin homologue from a
jumping spider. We found a spider opsin that shares amino acid homology and conserved amino acid residues with known peropsins.
The spider opsin-based pigment heterologously expressed in cultured cells exhibited photoisomerase-like isomerization characteristics
and a bistable nature. Based on the characteristics of both the amino acid homology and its photochemical properties, we concluded
that the spider opsin is the first protostome peropsin homologue. These results show that peropsin existed before the deuterostome–protostome
split like other members of the opsin family. In addition, the spider peropsin was localized to non-visual cells in the retina,
and fluorescence from reduced retinal chromophore was also observed in the region where peropsin was localized. These findings
provide the first demonstration that the peropsin can form a photosensitive pigment in vivo and underlie non-visual function. 相似文献
53.
Yamaguchi F Umeda Y Shimamoto S Tsuchiya M Tokumitsu H Tokuda M Kobayashi R 《The Journal of biological chemistry》2012,287(17):13787-13798
PP5 is a unique member of serine/threonine phosphatases comprising a regulatory tetratricopeptide repeat (TPR) domain and functions in signaling pathways that control many cellular responses. We reported previously that Ca(2+)/S100 proteins directly associate with several TPR-containing proteins and lead to dissociate the interactions of TPR proteins with their client proteins. Here, we identified protein phosphatase 5 (PP5) as a novel target of S100 proteins. In vitro binding studies demonstrated that S100A1, S100A2, S100A6, and S100B proteins specifically interact with PP5-TPR and inhibited the PP5-Hsp90 interaction. In addition, the S100 proteins activate PP5 by using a synthetic phosphopeptide and a physiological protein substrate, Tau. Overexpression of S100A1 in COS-7 cells induced dephosphorylation of Tau. However, S100A1 and permanently active S100P inhibited the apoptosis signal-regulating kinase 1 (ASK1) and PP5 interaction, resulting the inhibition of dephosphorylation of phospho-ASK1 by PP5. The association of the S100 proteins with PP5 provides a Ca(2+)-dependent regulatory mechanism for the phosphorylation status of intracellular proteins through the regulation of PP5 enzymatic activity or PP5-client protein interaction. 相似文献
54.
Koyanagi A Sekine C Yagita H 《Biochemical and biophysical research communications》2012,418(4):799-805
Notch plays multiple roles in T cell development in the thymus and T cell differentiation in the periphery. In order to systematically examine the role of Notch in T cell biology, we determined the cell surface expression of all Notch receptors and ligands on various populations of T cells by using a panel of specific monoclonal antibodies we recently established. Notch1 and Notch3 were upregulated at double-negative (DN) 2-DN4 stages of immature thymocytes, then downregulated on mature single-positive thymocytes and peripheral T cells, but were rapidly upregulated again upon activation. Notch2 was consistently expressed on T cells while Notch4 was not. Jagged1 and Jagged2 were expressed at double-positive stage of immature T cells. Jagged2 was also inducible on mature T cells upon activation. In contrast, no Delta-like (Dll) 1 or Dll4 expression was observed on T cells. These comprehensive profiling of the expression of Notch receptors and ligands would be informative to fully understand the role of individual Notch receptors and ligands in T cell development and differentiation. 相似文献
55.
Takekawa Y Saito M Wang C Qin T Ogawa M Kanemaru T Yoshida S 《Canadian journal of microbiology》2012,58(2):179-183
Legionella oakridgensis occasionally causes pneumonia in humans. We report here the characteristic morphology of intracellular microcolonies of L. oakridgensis OR-10 in infected epithelial cells. By light microscopy after Gimenez staining, the bacteria showed serpentine-like chain, disk-like conglomerate, and granular forms when they grew intracellularly in Vero cells, HeLa cells, and A549 cells. In a time-lapse study, we observed the progressive change from a serpentine-like chain form to a conglomerate form in Vero cells. Transmission electron microscopy showed that L. oakridgensis OR-10 proliferated both inside membrane structures and in the cytoplasm. Such highly serpentine chain growth has not been reported in any intracellular bacteria. Furthermore, these results imply that L. oakridgensis OR-10 may be proliferating inside the endoplasmic reticulum. 相似文献
56.
Y Takahashi T Koyanagi Y Suzuki Y Saga N Kanomata T Moriya M Suzuki Y Sato 《Molecular cancer research : MCR》2012,10(9):1135-1146
Vasohibin-1 (VASH1) is a VEGF-inducible endothelium-derived angiogenesis inhibitor and VASH2 is its homolog. Our previous analysis revealed that VASH1 is expressed in endothelial cells to terminate angiogenesis, whereas VASH2 is expressed in infiltrating mononuclear cells mobilized from bone marrow to promote angiogenesis in a mouse model of hypoxia-induced subcutaneous angiogenesis. To test the possible involvement of VASH2 in the tumor, we examined human ovarian cancer cells for the presence of VASH2. Immunohistochemical analysis revealed that VASH2 protein was preferentially detected in cancer cells of serous ovarian adenocarcinoma. We then used SKOV-3 and DISS, two representative human serous adenocarcinoma cell lines, and examined the role of VASH2 in the tumor. The knockdown of VASH2 showed little effect on the proliferation of cancer cells in vitro but notably inhibited tumor growth, peritoneal dissemination, and tumor angiogenesis in a murine xenograft model. Next, we stably transfected the human VASH2 gene into two types of murine tumor cells, EL-4 and MLTC-1, in which endogenous VASH2 was absent. When either EL-4 or MLTC-1 cells were inoculated into VASH2 (-/-) mice, the VASH2 transfectants formed bigger tumors when compared with the controls, and the tumor microvessel density was significantly increased. VASH2 stimulated the migration of endothelial cells, and its increased expression in cancer cells is related to the decrease of mir-200b. These results indicate that VASH2 expressed in serous ovarian carcinoma cells promoted tumor growth and peritoneal dissemination by promoting angiogenesis. Mol Cancer Res; 10(9); 1135-46. ?2012 AACR. 相似文献
57.
Human immunodeficiency virus type 1 (HIV-1)-infected macrophages damage mature neurons in the brain, although their effect on neuronal development has not been clarified. In this study, we show that HIV-1-infected macrophages produce factors that impair the development of neuronal precursor cells and that soluble viral protein R (Vpr) is one of the factors that has the ability to suppress axonal growth. Cell biological analysis revealed that extracellularly administered recombinant Vpr (rVpr) clearly accumulated in mitochondria where a Vpr-binding protein adenine nucleotide translocator localizes and also decreased the mitochondrial membrane potential, which led to ATP synthesis. The depletion of ATP synthesis reduced the transportation of mitochondria within neurites. This mitochondrial dysfunction inhibited axonal growth even when the frequency of apoptosis was not significant. We also found that point mutations of arginine (R) residues to alanine (A) residues at positions 73, 77, and 80 rendered rVpr incapable of causing mitochondrial membrane depolarization and axonal growth inhibition. Moreover, the Vpr-induced inhibition was suppressed after treatment with a ubiquinone analogue (ubiquinone-10). Our results suggest that soluble Vpr is a major viral factor that causes a disturbance in neuronal development through the induction of mitochondrial dysfunction. Since ubiquinone-10 protects the neuronal plasticity in vitro, it may be a therapeutic agent that can offer defense against HIV-1-associated neurological disease. 相似文献
58.
59.
In this report, unpublished and recent findings concerning the structure and function of the ascidian egg coat are compiled in context with fertilization. In the initial stage of ascidian fertilization, sperm interact with a complex egg investment that consists of a layer of follicle cells attached to an acellular vitelline coat. Increasing evidence exists that ascidian sperm are activated at their encounter with the follicle cells. The molecular basis of sperm-follicle cell interactions is discussed in context with sperm binding, membrane proteins and sperm bound glycosidase. The model that suggests a block to polyspermy established by glycosidase released from the follicle cells on fertilization is evaluated and compared with assured facts. Although a number of questions remain to be answered, our recent findings that a cloned beta-hexosaminidase from P. mammillata binds exclusively to the follicle cells of unfertilized but not fertilized eggs, indicates that the follicle cells participate in the block to polyspermy. A dual function, mediating sperm activation and a block to polyspermy attributes to the ascidian follicle cells a key position in fertilization. 相似文献
60.
Urano E Kariya Y Futahashi Y Ichikawa R Hamatake M Fukazawa H Morikawa Y Yoshida T Koyanagi Y Yamamoto N Komano J 《FEBS letters》2008,582(29):4053-4058
We conducted a phenotypic cDNA screening using a T cell line-based assay to identify human genes that render cells resistant to human immunodeficiency virus type 1 (HIV-1). We isolated potential HIV-1 resistance genes, including the carboxy terminal domain (CTD) of bromodomain-containing protein 4 (Brd4). Expression of GFP-Brd4-CTD was tolerated in MT-4 and Jurkat cells in which HIV-1 replication was markedly inhibited. We provide direct experimental data demonstrating that Brd4-CTD serves as a specific inhibitor of HIV-1 replication in T cells. Our method is a powerful tool for the identification of host factors that regulate HIV-1 replication in T cells. 相似文献