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排序方式: 共有474条查询结果,搜索用时 15 毫秒
31.
32.
Endothelium of the cerebral blood microvessels, which constitutes the major component of the blood-brain barrier, controls leukocyte and metastatic cancer cell adhesion and trafficking into the brain parenchyma. In this study, using rat primary brain microvascular endothelial cells (BMEC), we demonstrate that the vascular endothelial growth factor (VEGF), a potent promoter of angiogenesis, up-regulates the expression of the intracellular adhesion molecule-1 (ICAM-1) through a novel pathway that includes phosphatidylinositol 3 OH-kinase (PI3K), AKT, and nitric oxide (NO), resulting in the migration of BMEC. Upon VEGF treatment, AKT is phosphorylated in a PI3K-dependent manner. AKT activation leads to NO production and release and activation-deficient AKT attenuates NO production stimulated by VEGF. Transfection of the constitutive myr-AKT construct significantly increased basal NO release in BMEC. In these cells, VEGF and the endothelium-derived NO synergistically up-regulated the expression of ICAM-1, which was mediated by the PI3K pathway. This activity was blocked by the PI3K-specific inhibitor, wortmannin. Furthermore, VEGF and NO significantly increased BMEC migration, which was mediated by the up-regulation of ICAM-1 expression and was dependent on the integrity of the PI3K/AKT/NO pathway. This effect was abolished by wortmannin, by the specific ICAM-1 antibody, by the specific inhibitor of NO synthase, N(G)-l-monomethyl-arginine (l-NMMA) or by a combination of wortmannin, ICAM-1 antibody, and l-NMMA. These findings demonstrate that the angiogenic factor VEGF up-regulates ICAM-1 expression and signals to ICAM-1 as an effector molecule through the PI3K/AKT/NO pathway, which leads to brain microvessel endothelial cell migration. These observations may contribute to a better understanding of BMEC angiogenesis and the physiological as well as pathophysiological function of the blood-brain barrier, whose integrity is crucial for normal brain function. 相似文献
33.
Characterization of the tyrosine kinases RAFTK/Pyk2 and FAK in nerve growth factor-induced neuronal differentiation 总被引:2,自引:0,他引:2
The related adhesion focal tyrosine kinase (RAFTK), a member of the focal adhesion kinase (FAK) family and highly expressed in brain, is a key mediator of various extracellular signals that elevate intracellular Ca(2+) concentration. We investigated RAFTK and FAK signaling upon nerve growth factor (NGF) stimulation of PC12 cells. NGF induced the tyrosine phosphorylation of RAFTK in a time- and dose-dependent manner, whereas no change in the tyrosine phosphorylation of FAK was observed. Chemical inhibition showed that RAFTK phosphorylation was inhibited by blocking phospholipase Cgamma activity or intracellular Ca(2+). Blocking of extracellular Ca(2+) or phosphatidylinositol 3-kinase activity partially reduced the phosphorylation of RAFTK. In addition, disruption of actin polymerization abolished RAFTK phosphorylation, indicating that an intact actin-based cytoskeletal organization is required for RAFTK phosphorylation. The focal adhesion molecule paxillin was co-immunoprecipitated with RAFTK, and its tyrosine phosphorylation was increased in a Ca(2+)-dependent manner upon NGF stimulation. Confocal microscopic analysis demonstrated that RAFTK translocated from the cytoplasm to potential neurite initiation sites at the cell periphery, where RAFTK co-localized with paxillin and bundled actin in the early phase (within 5 min) of NGF stimulation, whereas FAK co-localized with paxillin at "point contacts," which are the primary cell adhesion sites in neuronal cells. Significant distribution of RAFTK was observed in the neurites and growth cones of differentiated PC12 cells. Furthermore, potassium depolarization induced the tyrosine phosphorylation of both RAFTK and paxillin in an intracellular Ca(2+)-dependent manner in the differentiated PC12 cells. Taken together, these results demonstrate that RAFTK is involved in NGF-induced cytoskeletal organization and may play a role in neurite and growth cone function(s). 相似文献
34.
Ganju RK Brubaker SA Chernock RD Avraham S Groopman JE 《The Journal of biological chemistry》2000,275(23):17263-17268
The beta-chemokine receptor CCR5 has been shown to modulate cell migration, proliferation, and immune functions and to serve as a co-receptor for the human immunodeficiency virus. We and others have shown that CCR5 activates related adhesion focal tyrosine kinase (RAFTK)/Pyk2/CAK-beta. In this study, we further characterize the signaling molecules activated by CCR5 upon binding to its cognate ligand, macrophage inflammatory protein-1beta (MIP1beta). We observed enhanced tyrosine phosphorylation of the phosphatases SHP1 and SHP2 upon MIP1beta stimulation of CCR5 L1.2 transfectants and T-cells derived from peripheral blood mononuclear cells. Furthermore, we observed that SHP1 associated with RAFTK. However, using a dominant-negative phosphatase-binding mutant of RAFTK (RAFTK(m906)), we found that RAFTK does not mediate SHP1 or SHP2 phosphorylation. SHP1 and SHP2 also associated with the adaptor protein Grb2 and the Src-related kinase Syk. Pretreatment of CCR5 L1.2 transfectants or T-cells with the phosphatase inhibitor orthovanadate markedly abolished MIP1beta-induced chemotaxis. Syk was also activated upon MIP1beta stimulation of CCR5 L1.2 transfectants or T-cells and associated with RAFTK. Overexpression of a dominant-negative Src-binding mutant of RAFTK (RAFTK(m402)) significantly attenuated Syk activation, whereas overexpression of wild-type RAFTK enhanced Syk activity, indicating that RAFTK acts upstream of CCR5-mediated Syk activation. Taken together, these results suggest that MIP1beta stimulation mediated by CCR5 induces the formation of a signaling complex consisting of RAFTK, Syk, SHP1, and Grb2. 相似文献
35.
Genomic organization, chromosomal localization and regulation of expression of the neuronal nuclear matrix protein NRP/B in human brain tumors 总被引:5,自引:0,他引:5
The nuclear matrix and its role in cell physiology are largely unknown, and the discovery of any matrix constituent whose expression is tissue- and/or cell-specific offers a new avenue of exploration. Studies of the novel neuronal nuclear matrix protein, NRP/B, reveal that it is an early and highly specific marker of neuronal induction and development in vertebrates, since its expression is restricted mainly to the developing and mature nervous system. These studies also show that NRP/B is involved in neuronal differentiation. To further examine the structure-function of NRP/B, we have cloned and characterized the murine Nrp/b gene. The murine gene consists of four exons interrupted by three introns that span 7.6kb of DNA. The complete open reading frame is localized in exon 3, suggesting that NRP/B is highly conserved during evolution. Chromosomal analysis shows that NRP/B is localized to chromosome 13 in mouse and chromosome 5q12-13 in human.Since our previous studies demonstrated that NRP/B is expressed in primary hippocampal neurons but not in primary astrocytes, we have characterized NRP/B mRNA and protein expression in various brain cell lines and in human brain tumors. Abundant expression of NRP/B mRNA and protein was observed in human neuroblastoma cell lines (IMR32, SKN-MC, SKN-SH), in glioblastoma cell lines (A172, T98G, U87-MG, U118-MG, U138-MG, and U373-MG), in neuroglioma (H4) and astrocytoma cell lines (CCF-STTG1 and SW1088). Confocal analysis of NRP/B in U87-MG glioblastoma cells indicated nuclear localization of NRP/B. NRP/B expression was also observed in human primary brain tumors including glioblastoma multiformae and astrocytomas (total of five cases). These results suggest that NRP/B expression is upregulated in human brain tumors including glioblastomas and astrocytomas, while under normal conditions NRP/B expression is restricted to neurons. This study implicates a role for NRP/B in brain tumor development. 相似文献
36.
A Shitzer S Bellomo L A Stroschein R R Gonzalez K B Pandolf 《Journal of biomechanical engineering》1998,120(3):389-394
The thermal response of fingers exposed to cold weather conditions has been simulated. Energy balance equations were formulated, in a former study, for the tissue layers and the arterial, venous, and capillary blood vessels. The equations were solved by a finite difference scheme using the Thomas algorithm and the method of alternating directions. At this stage of development the model does not include any autonomic control functions. Model simulations assumed an electrical heating element to be embedded in the glove layers applied on the finger. A 1.3 W power input was calculated for maintaining finger temperatures at their pre-cold exposure level in a 0 degree C environment. Alternate assumptions of nutritional (low) and basal (high) blood flows in the finger demonstrated the dominance of this factor in maintaining finger temperatures at comfortable levels. Simulated exposures to still and windy air, at 4.17 m/s (15 km/h), indicated the profound chilling effects of wind on fingers in cold environments. Finally, the effects of variable blood flow in the finger, known as "cold-induced vasodilatation," were also investigated. Blood flow variations were assumed to be represented by periodic, symmetric triangular waves allowing for gradual opening-closing cycles of blood supply to the tip of the finger. Results of this part of the simulation were compared with measured records of bare finger temperatures. Good conformity was obtained for a plausible pattern of change in blood flow, which was assumed to be provided in its entirety to the tip of the finger alone. 相似文献
37.
Yael Ben Shabat Avraham Shitzer Dusan Fiala 《International journal of biometeorology》2014,58(6):1007-1015
Wind chill equivalent temperatures (WCETs) were estimated by a modified Fiala’s whole body thermoregulation model of a clothed person. Facial convective heat exchange coefficients applied in the computations concurrently with environmental radiation effects were taken from a recently derived human-based correlation. Apart from these, the analysis followed the methodology used in the derivation of the currently used wind chill charts. WCET values are summarized by the following equation: $$ \mathrm{WCET}=12.87+0.5334\ast {T}_o-\left(12.66-0.4414\ast {T}_o\right)\ast {U}_{reported}{}^{0.1228} $$ Results indicate consistently lower estimated facial skin temperatures and consequently higher WCETs than those listed in the literature and used by the North American weather services. Calculated dynamic facial skin temperatures were additionally applied in the estimation of probabilities for the occurrence of risks of frostbite. Predicted weather combinations for probabilities of “Practically no risk of frostbite for most people,” for less than 5 % risk at wind speeds above 40 km h?1, were shown to occur at air temperatures above ?10 °C compared to the currently published air temperature of ?15 °C. At air temperatures below ?35 °C, the presently calculated weather combination of 40 km h?1/?35 °C, at which the transition for risks to incur a frostbite in less than 2 min, is less conservative than that published: 60 km h?1/?40 °C. The present results introduce a fundamentally improved scientific basis for estimating facial skin temperatures, wind chill temperatures and risk probabilities for frostbites over those currently practiced. 相似文献
38.
39.
Nangia-Makker P Nakahara S Hogan V Raz A 《Journal of bioenergetics and biomembranes》2007,39(1):79-84
During the past decade, extensive progress has been made toward understanding the molecular basis for the regulation of apoptosis.
In mammalian cells undergoing apoptosis, two distinct mechanisms or pathways are operated and are triggered by cell death
stimuli from intra- or extra-cellular environments, namely the intrinsic or extrinsic pathways, resulting in mitochondrial
membrane depolarization. Several lines of evidence from our laboratories and others have indicated that galectin-3 plays an
important role in these pathways by binding to various ligands. Here the authors provide a brief discussion on the role of
endogenous or extra-cellular galectin-3 in the regulation of apoptosis and how it could be used as a therapeutic target using
natural plant products as its functional inhibitors. 相似文献
40.
Jiang S Seng S Avraham HK Fu Y Avraham S 《The Journal of biological chemistry》2007,282(16):12319-12329
Oligodendrocytes (OLGs) are generated by progenitor cells that are committed to differentiating into myelin-forming cells of the central nervous system. Rearrangement of the cytoskeleton leading to the extension of cellular processes is essential for the myelination of axons by OLGs. Here, we have characterized a new member of the Kelch-related protein family termed MRP2 (for Mayven-related protein 2) that is specifically expressed in brain. MRP2/KLHL1 is expressed in oligodendrocyte precursors and mature OLGs, and its expression is up-regulated during OLG differentiation. MRP2/KLHL1 expression was abundant during the specific stages of oligodendrocyte development, as identified by A2B5-, O4-, and O1-specific oligodendrocyte markers. MRP2/KLHL1 was localized in the cytoplasm and along the cell processes. Moreover, a direct endogenous association of MRP2/KLHL1 with actin was observed, which was significantly increased in differentiated OLGs compared with undifferentiated OLGs. Overexpression of MRP2/KLHL1 resulted in a significant increase in the process extension of rat OLGs, whereas MRP2/KLHL1 antisense reduced the process length of primary rat OLGs. Furthermore, murine OLGs isolated from MRP2/KLHL1 transgenic mice showed a significant increase in the process extension of OLGs compared with control wild-type murine OLGs. These studies provide insights into the role of MRP2/KLHL1, through its interaction with actin, in the process elongation of OLGs. 相似文献