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51.
VEGF-induced vascular permeability is mediated by FAK 总被引:1,自引:0,他引:1
Chen XL Nam JO Jean C Lawson C Walsh CT Goka E Lim ST Tomar A Tancioni I Uryu S Guan JL Acevedo LM Weis SM Cheresh DA Schlaepfer DD 《Developmental cell》2012,22(1):146-157
Endothelial cells (ECs) form cell-cell adhesive junctional structures maintaining vascular integrity. This barrier is dynamically regulated by vascular endothelial growth factor (VEGF) receptor signaling. We created an inducible knockin mouse model to study the contribution of the integrin-associated focal adhesion tyrosine kinase (FAK) signaling on vascular function. Here we show that genetic or pharmacological FAK inhibition in ECs prevents VEGF-stimulated permeability downstream of VEGF receptor or Src tyrosine kinase activation in vivo. VEGF promotes tension-independent FAK activation, rapid FAK localization to cell-cell junctions, binding of the FAK FERM domain to the vascular endothelial cadherin (VE-cadherin) cytoplasmic tail, and direct FAK phosphorylation of β-catenin at tyrosine-142 (Y142) facilitating VE-cadherin-β-catenin dissociation and EC junctional breakdown. Kinase inhibited FAK is in a closed conformation that prevents VE-cadherin association and limits VEGF-stimulated β-catenin Y142 phosphorylation. Our studies establish a role for FAK as an essential signaling switch within ECs regulating adherens junction dynamics. 相似文献
52.
A total of 492 cattle sera was screened by IgG-ELISA against Neospora caninum (Nc-1 strain and a Korean isolate, KBA-2) and Toxoplasma gondii. Out of 492, 113 sera (23.0%) reacted positively to either Nc-1 or KBA-2 strains of N. caninum. Among the 113 positive sera, 92 sera (81.4%) reacted with antigens of both strains, but 6 sera (5.3%) with Nc-1 and 15 sera (13.3%) with KBA-2 strain only. And with T. gondii antigen, 6 sera (1.2%) were positive but all reacted with N. caninum antigen also. Western blot revealed typical binding pattern according to ELISA values, such that high OD group reacted specifically to the major surface proteins including 43 kDa protein. Seroprevalence of 23.0% indicates that neosporosis seemed to be one of major causes of abortion in cattle. It is suggested here to establish more epidemiological researches nationwide systematically. 相似文献
53.
Bichen Zhang Kalina Lapenta Qi Wang Jin Hyun Nam Dongjun Chung Marie E. Robert Michael H. Nathanson Xiaoyong Yang 《The Journal of biological chemistry》2021,297(1)
Liver fibrosis is a common characteristic of chronic liver diseases. The activation of hepatic stellate cells (HSCs) plays a key role in fibrogenesis in response to liver injury, yet the mechanism by which damaged hepatocytes modulate the activation of HSCs is poorly understood. Our previous studies have established that liver-specific deletion of O-GlcNAc transferase (OGT)leads to hepatocyte necroptosis and spontaneous fibrosis. Here, we report that OGT-deficient hepatocytes secrete trefoil factor 2 (TFF2) that activates HSCs and contributes to the fibrogenic process. The expression and secretion of TFF2 are induced in OGT-deficient hepatocytes but not in WT hepatocytes. TFF2 activates the platelet-derived growth factor receptor beta signaling pathway that promotes the proliferation and migration of primary HSCs. TFF2 protein expression is elevated in mice with carbon tetrachloride-induced liver injury. These findings identify TFF2 as a novel factor that mediates intercellular signaling between hepatocytes and HSCs and suggest a role of the hepatic OGT–TFF2 axis in the process of fibrogenesis. 相似文献
54.
Hae Mi Joo Su Jin Kang Seon Young Nam Kwang Hee Yang Cha Soon Kim In Kyung Lee Ji Young Kim 《PloS one》2015,10(8)
Ionizing radiation has different biological effects according to dose and dose rate. In particular, the biological effect of low-dose radiation is unclear. Low-dose whole-body gamma irradiation activates immune responses in several ways. However, the effects and mechanism of low-dose radiation on allergic responses remain poorly understood. Previously, we reported that low-dose ionizing radiation inhibits mediator release in IgE-mediated RBL-2H3 mast cell activation. In this study, to have any physiological relevance, we investigated whether low-dose radiation inhibits allergic responses in activated human mast cells (HMC-1(5C6) and LAD2 cells), mouse models of passive cutaneous anaphylaxis and the late-phase cutaneous response. High-dose radiation induced cell death, but low-dose ionizing radiation of <0.5 Gy did not induce mast cell death. Low-dose ionizing radiation that did not induce cell death significantly suppressed mediator release from human mast cells (HMC-1(5C6) and LAD2 cells) that were activated by antigen-antibody reaction. To determine the inhibitory mechanism of mediator released by low-dose ionizing radiation, we examined the phosphorylation of intracellular signaling molecules such as Lyn, Syk, phospholipase Cγ, and protein kinase C, as well as the intracellular free Ca2+ concentration ([Ca2+]i). The phosphorylation of signaling molecules and [Ca2+]i following stimulation of FcεRI receptors was inhibited by low dose ionizing radiation. In agreement with its in vitro effect, ionizing radiation also significantly inhibited inflammatory cells infiltration, cytokine mRNA expression (TNF-α, IL-4, IL-13), and symptoms of passive cutaneous anaphylaxis reaction and the late-phase cutaneous response in anti-dinitrophenyl IgE-sensitized mice. These results indicate that ionizing radiation inhibits both mast cell-mediated immediate- and delayed-type allergic reactions in vivo and in vitro. 相似文献
55.
Zn‐Air Batteries: Composites of a Prussian Blue Analogue and Gelatin‐Derived Nitrogen‐Doped Carbon‐Supported Porous Spinel Oxides as Electrocatalysts for a Zn–Air Battery (Adv. Energy Mater. 22/2016) 下载免费PDF全文
56.
Kim D Kim SN Baik KS Park SC Lim CH Kim JO Shin TS Oh MJ Seong CN 《Journal of microbiology (Seoul, Korea)》2011,49(1):141-145
A metagenomic fosmid library was constructed using genomic DNA isolated from abalone intestine. Screening of a library of
3,840 clones revealed a 36 kb insert of a cellulase positive clone (pAMHElO). A shotgun clone library was constructed using
the positive clone (pAMHElO) and further screening of 3,840 shotgun clones with an approximately 5 kb insert size using a
Congo red overlay revealed only one cellulase positive clone (pAMHL9). The pAMHL9 consisted of a 5,293-bp DNA sequence and
three open reading frames (ORFs). Among the three ORFs, cellulase activity was only shown in the recombinant protein (CelAMll)
coded by ORF3, which showed 100% identity with outer membrane protein A from Vibrio alginolyticus 12G01, but no significant sequence homology to known cellulases. The expressed protein (CelAMll) has a molecular weight of
approximately 37 kDa and the highest CMC hydrolysis activity was observed at pH 7.0 and 37°C. The carboxymethyl cellulase
activity was determined by zymogram active staining and different degraded product profiles for CelAMll were obtained when
cellotetraose and cellopentaose were used as the substrates, while no substrate hydrolysis was observed on oligosaccharides
such as cellobiose and cellotriose. 相似文献
57.
Han Gil Choi Ji Hee Lee Young-Kug Choo Kyu-Yun Chai Young Sik Kim Jung-Soo Han Anchana Prathep Ki Wan Nam 《Phycological Research》2006,54(4):302-307
The seasonal growth and reproductive phenology of Neorhodomela aculeata (Perestenko) Masuda and Ceramium kondoi Yendo, and the food preferences of herbivorous snails were examined to elucidate (i) why snails select the fronds of N. aculeata for their habitat; and (ii) the survival strategies of the two red algae under grazing pressures. The maximal lengths and weights of both algal species were recorded for each season over a 12‐month period beginning with the spring of 2003. C. kondoi grew in length at a faster rate than N. aculeate, whereas the turf alga N. aculeata produced new branches from the tips of broken branches. The reproductive period of C. kondoi was between the spring and summer but the reproductive organs of N. aculeata were observed throughout the year. The algal loss rate of fresh N. aculeata to snails was low but snails had a food preference for N. aculeata when compared to C. kondoi in an artificial food experiment. These results indicate that snails may adapt to chemical compounds characteristic of N. aculeata and that the alga further reduces predation damage by its structural resistance. In conclusion, the survival strategies of C. kondoi appear to be rapid growth, seasonal sexual reproduction, and a delicately branched frond morphology that reduces stable feeding patterns of its predators plus high tissue nitrogen content, whereas the survival strategy of N. aculeata includes regenerative growth responses, structural toughness and chemical defenses while under the grazing pressure of herbivorous snails. 相似文献
58.
Induction of endothelial apoptosis by 4-hydroxyhexenal. 总被引:1,自引:0,他引:1
Ji Young Lee Jeong Hwan Je Dae Hyun Kim Sang Woon Chung Yani Zou Nam Deuk Kim Mie Ae Yoo Hyung Suck Baik Byung Pal Yu Hae Young Chung 《European journal of biochemistry》2004,271(7):1339-1347
Lipid peroxidation and its products such as 4-hydroxy-2-nonenal (HNE) and 4-hydroxyhexenal (HHE) are known to affect redox balance during aging and various degenerative processes, including vascular dysfunction. Deterioration of the endothelial cells that line the vascular wall is known to be an underlying cause of vascular dysfunction. At present, little is known about the mechanism by which HHE induces endothelial cell death (i.e. apoptosis), although HNE-induced apoptotic cell death has been reported. The aim of this study was to determine whether apoptosis induced by HHE in endothelial cells involves peroxynitrite (ONOO(-)). Our results show that in endothelial cells HHE triggers apoptotic cell death by inducing apoptotic Bax coupled with a decrease in anti-apoptotic Bcl-2. Results show that HHE induces reactive oxygen species (ROS), nitric oxide, and ONOO(-) generation, leading to redox imbalance. Furthermore, the antioxidant N-acetyl cysteine, ROS scavenger, and penicillamine, an ONOO(-) scavenger, were found to block HHE-mediated apoptosis. We used confocal laser microscopy to estimate the ability of these inhibitors to attenuate HHE-induced intracellular ONOO(-) levels thus confirming the oxidative mediation of apoptosis in endothelial cells. These findings strongly suggest that accumulated HHE triggers reactive species-mediated endothelial apoptosis, leading to vascular dysfunction as well as vascular aging. During aging, increased lipid peroxidation and its associated production of HHE may exacerbate the weakened redox balance, leading to various chronic degenerative processes including vascular dysfunction. 相似文献
59.
Yun BY Jun SY Kim NA Yoon BY Piao S Park SH Jeong SH Lee H Ha NC 《Biochemical and biophysical research communications》2011,416(1-2):92-98
Glycoside hydrolase family 4 (GH4) represents an unusual group of glucosidases with a requirement for NAD(+), Mn(2+), and reducing conditions. We found a putative α-glucosidase belonging to GH4 in hyperthermophilic Gram-negative bacterium Thermotoga neapolitana. In this study, we recombinantly expressed the putative α-glycosidase from T. neapolitana, and determined the crystal structure of the protein at a resolution of 2.0? in the presence of Mn(2+) but in the absence of NAD(+). The structure showed the dimeric assembly and the Mn(2+) coordination that other GH4 enzymes share. In comparison, we observed structural changes in T. neapolitana α-glucosidase by the binding of NAD(+), which also increased the thermostability. Numerous arginine-mediated salt-bridges were observed in the structure, and we confirmed that the salt bridges correlated with the thermostability of the proteins. Disruption of the salt bridge that linked N-terminal and C-terminal parts at the surface dramatically decreased the thermostability. A mutation that changed the internal salt bridge to a hydrogen bond also decreased the thermostability of the protein. This study will help us to understand the function of the putative glucosidase and the structural features that affect the thermostability of the protein. 相似文献
60.