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71.
The transient receptor potential (TRPC) family of Ca2 + permeable, non-selective cation channels is abundantly expressed in the brain, and can function as store-operated (SOC) and store-independent channels depending on their interaction with the ER Ca2 + sensor STIM1. TRPC1 and TRPC5 have critical roles in neurite outgrowth, however which of their functions regulate neurite outgrowth is unknown. In this study, we investigated the effects of TRPC channels and their STIM1-induced SOC activity on neurite outgrowth of PC12 cells. We report that PC12 cell differentiation down-regulates TRPC5 expression, whereas TRPC1 expression is retained. TRPC1 and TRPC5 interact with STIM1 through the STIM1 ERM domain. Transfection of TRPC1 and TRPC5 increased the receptor-activated Ca2 + influx that was markedly augmented by the co-expression of STIM1. Topical expression of TRPC1 in PC12 cells markedly increased neurite outgrowth while that of TRPC5 suppressed neurite outgrowth. Suppression of neurite outgrowth by TRPC5 requires the channel function of TRPC5. However, strikingly, multiple lines of evidence show that the TRPC1-induced neurite outgrowth was independent of TRPC1-mediated Ca2 + influx. Thus, a) TRPC1 and TRPC5 similarly increased Ca2 + influx but only TRPC1 induced neurite outgrowth, b) the constitutively STIM1D76A mutant that activates Ca2 + influx by TRPC and Orai channels did not increase neurite outgrowth, c) co-expression of TRPC5 with TRPC1 suppressed the effect of TRPC1 on neurite outgrowth, d) and most notable, channel-dead pore mutant of TRPC1 increased neurite outgrowth to the same extent as TRPC1WT. Suppression of TRPC1-induced neurite outgrowth by TRPC5 was due to a marked reduction in the surface expression of TRPC1. We conclude that the regulation of neurite outgrowth by TRPC1 is independent of Ca2 + influx and TRPC1-promoted neurite outgrowth depends on the surface expression of TRPC1. It is likely that TRPC1 acts as a scaffold at the cell surface to assemble a signaling complex to stimulate neurite outgrowth. 相似文献
72.
KW Kwon H Park KH Song JC Choi H Ahn MJ Park KY Suh J Doh 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(5):2266-2273
T cells navigate a wide variety of tissues and organs for immune surveillance and effector functions. Although nanoscale topographical structures of extracellular matrices and stromal/endothelial cell surfaces in local tissues may guide the migration of T cells, there has been little opportunity to study how nanoscale topographical features affect T cell migration. In this study, we systematically investigated mechanisms of nanotopography-guided migration of T cells using nanoscale ridge/groove surfaces. The velocity and directionality of T cells on these nanostructured surfaces were quantitatively assessed with and without confinement, which is a key property of three-dimensional interstitial tissue spaces for leukocyte motility. Depending on the confinement, T cells exhibited different mechanisms for nanotopography-guided migration. Without confinement, actin polymerization-driven leading edge protrusion was guided toward the direction of nanogrooves via integrin-mediated adhesion. In contrast, T cells under confinement appeared to migrate along the direction of nanogrooves purely by mechanical effects, and integrin-mediated adhesion was dispensable. Therefore, surface nanotopography may play a prominent role in generating migratory patterns for T cells. Because the majority of cells in periphery migrate along the topography of extracellular matrices with much lower motility than T cells, nanotopography-guided migration of T cells would be an important strategy to efficiently perform cell-mediated immune responses by increasing chances of encountering other cells within a given amount of time. 相似文献
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Abstract. Estimation of potential annual direct incident radiation has traditionally required numerical integration with simulation models. As an alternative, we present convenient equations for use in spreadsheet, GIS, and database applications. Input variables are latitude, slope, and aspect. The equations apply to 0–60° north latitude, slopes from 0–90°, and all aspects. By transforming aspect, the equations can also be applied as an index of heat load, symmetrical about a northeast to southwest axis. 相似文献
76.
Kim KY Bang S Han S Nguyen YH Kang TM Kang KW Hwang SW 《Biochemical and biophysical research communications》2008,370(2):295-300
Menthol, cinnamaldehyde, and camphor are activators for temperature-sensitive transient receptor potential ion channels (thermoTRPs). Here we found that these three compounds inhibit the phospholipase C (PLC) signaling. P2Y purinoceptor-mediated or histamine receptor-mediated cytosolic calcium mobilization through the PLC pathway was significantly suppressed by menthol, cinnamaldehyde, and camphor. Experiments using a fluorescent pleckstrin homology domain of PLCδ1 and IP1 accumulation assays demonstrated that direct inhibition of PLC activity occurred upon the addition of the sensory compounds. P2Y receptor-mediated PLC activation is part of the mechanism of platelet aggregation. The three compounds inhibited ADP-induced platelet aggregation. Calcium influx studies showed that thermoTRPs do not function in platelets, suggesting that the anti-aggregation effect is independent of thermoTRP activity. These results suggest that menthol, cinnamaldehyde, and camphor are able to modify PLC signaling and that those effects may lead to changes in cellular functions. This study also identifies new types of compounds that could potentially modulate platelet-related pathological events. 相似文献
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Production of biologically active human granulocyte colony stimulating factor in the milk of transgenic goat 总被引:1,自引:1,他引:0
Ko JH Lee CS Kim KH Pang MG Koo JS Fang N Koo DB Oh KB Youn WS Zheng GD Park JS Kim SJ Han YM Choi IY Lim J Shin ST Jin SW Lee KK Yoo OJ 《Transgenic research》2000,9(3):215-222
We have developed a transgenic female goat harboring goat beta-casein promoter/human granulocyte colony stimulating factor (G-CSF) fusion gene by microinjection into fertilized one-cell goat zygotes. Human G-CSF was produced at levels of up to 50g/ml in transgenic goat milk. Its biological activity was equivalent to recombinant human G-CSF expressed from Chinese hamster ovary (CHO) cell when assayed using in vitro HL-60 cell proliferation. Human G-CSF from transgenic goat milk increased the total number of white blood cells in C57BL/6N mice with leucopenia induced by cyclophosphamide (CPA). The secreted human G-CSF was glycosylated although the degree of O-glycosylation was lower compared to CHO cell-derived human G-CSF. 相似文献
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Finlay D Healy V Furlong F O'Connell FC Keon NK Martin F 《Cell death and differentiation》2000,7(3):302-313
Mammary epithelial cells in primary cell culture require both growth factors and specific extracellular matrix (ECM)-attachment for survival. Here we demonstrate for the first time that inhibition of the ECM-induced Erk 1/Erk 2 (p42/44 MAPK) pathway, by PD 98059, leads to apoptosis in these cells. Associated with this cell death is a possible compensatory signalling through the p38 MAP kinase pathway the inhibition of which, by SB 203580, leads to a more rapid onset of apoptosis. This provides evidence for a hitherto undescribed Erk 1/Erk 2 to p38 MAP kinase pathway 'cross-talk' that is essential for the survival of these cells. The cell death associated with inhibition of these two MAP kinase pathways however, occurred in the presence of insulin that activates the classical PI-3 kinase-dependent Akt/PKB survival signals and Akt phosphorylation. Cell death induced by inhibition of the MAP kinase pathways did not affect Akt phosphorylation and may, thus, be independent of PI-3 kinase signalling. 相似文献