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991.
Fernández-Fernández JM Nobles M Currid A Vázquez E Valverde MA 《American journal of physiology. Cell physiology》2002,283(6):C1705-C1714
The cell regulatory volume decrease (RVD) response triggered by hypotonic solutions is mainly achieved by the coordinated activity of Cl- and K+ channels. We now describe the molecular nature of the K(+) channels involved in the RVD response of the human bronchial epithelial (HBE) cell line 16HBE14o-. These cells, under isotonic conditions, present a K+ current consistent with the activity of maxi K+ channels, confirmed by RT-PCR and Western blot. Single-channel and whole cell maxi K+ currents were readily and reversibly activated following the exposure of HBE cells to a 28% hypotonic solution. Both maxi K+ current activation and RVD response showed calcium dependency, inhibition by TEA, Ba2+, iberiotoxin, and the cationic channel blocker Gd3+ but were insensitive to clofilium, clotrimazole, and apamin. The presence of the recently cloned swelling-activated, Gd3+-sensitive cation channels (TRPV4, also known as OTRPC4, TRP12, or VR-OAC) was detected by RT-PCR in HBE cells. This channel, TRPV4, which senses changes in volume, might provide the pathway for Ca2+ influx under hypotonic solutions and, consequently, for the activation of maxi K+ channels. 相似文献
992.
Transthyretin (TTR) is a plasma and cerebrospinal fluid (CSF)-circulating homotetrameric protein. More than 100 point mutations have been identified in the TTR gene and several are related with amyloid diseases. Here we focused our attention in the TTR L12P variant associated with severe peripheral neuropathy and leptomeningeal amyloidosis. By using different cell lines derived from tissues specialized on TTR synthesis, such as the hepatocyte and the choroid plexus expressing WT, V30M, or L12P TTR variants we analyzed secretion, intracellular aggregation and degradation patterns. Also, we used liver-specific AAV gene transfer to assess expression of the L12P variant in vivo. We found the following: (i) decreased secretion with intracellular aggregation of TTR L12P in hepatoma cells relative to WT and V30M variant; this differential property of TTR L12P variant was also observed in mice injected with L12P AAV vector; (ii) differential N-glycosylation pattern of L12P variant in hepatoma cell lysates, conditioned media and mouse sera, which might represent an escape mechanism from ERAD degradation; (iii) intracellular L12P TTR aggregates mainly localized to lysosomes in cultured cells and liver; and (iv) none of the above findings were present in choroid plexus derived cells, suggesting particular secretion/quality control mechanisms that might contribute to leptomeningeal amyloidosis associated with the L12P variant. These observations open new avenues for the treatment of TTR associated leptomeningeal amyloidosis. 相似文献
993.
Hideo Satsu Marie-Therese Schaeffer Miguel Guerrero Adrian Saldana Christina Eberhart Peter Hodder Charmagne Cayanan Stephan Schürer Barun Bhhatarai Ed Roberts Hugh Rosen Steven J. Brown 《Bioorganic & medicinal chemistry》2013,21(17):5373-5382
Molecular probe tool compounds for the Sphingosine 1-phosphate receptor 2 (S1PR2) are important for investigating the multiple biological processes in which the S1PR2 receptor has been implicated. Amongst these are NF-κB-mediated tumor cell survival and fibroblast chemotaxis to fibronectin. Here we report our efforts to identify selective chemical probes for S1PR2 and their characterization. We employed high throughput screening to identify two compounds which activate the S1PR2 receptor. SAR optimization led to compounds with high nanomolar potency. These compounds, XAX-162 and CYM-5520, are highly selective and do not activate other S1P receptors. Binding of CYM-5520 is not competitive with the antagonist JTE-013. Mutation of receptor residues responsible for binding to the zwitterionic headgroup of sphingosine 1-phosphate (S1P) abolishes S1P activation of the receptor, but not activation by CYM-5520. Competitive binding experiments with radiolabeled S1P demonstrate that CYM-5520 is an allosteric agonist and does not displace the native ligand. Computational modeling suggests that CYM-5520 binds lower in the orthosteric binding pocket, and that co-binding with S1P is energetically well tolerated. In summary, we have identified an allosteric S1PR2 selective agonist compound. 相似文献
994.
Leopoldo Naranjo-Brice?o Beatriz Pernía Mayamaru Guerra Jhonny R Demey ángela De Sisto Ysvic Inojosa Meralys González Emidio Fusella Miguel Freites Francisco Yegres 《Microbial biotechnology》2013,6(6):720-730
Large amount of drilling waste associated with the expansion of the Orinoco Oil Belt (OOB), the biggest proven reserve of extra-heavy crude oil (EHCO) worldwide, is usually impregnated with EHCO and highly salinized water-based drilling fluids. Oxidative exoenzymes (OE) of the lignin-degrading enzyme system (LDS) of fungi catalyse the oxidation of a wide range of toxic pollutants. However, very little evidences on fungal degradation or biotransformation of EHCO have been reported, which contain high amounts of asphaltenes and its biodegradation rate is very limited. The aims of this work were to study the ability of Pestalotiopsis palmarum BM-04 to synthesize OE, its potential to biotransform EHCO and to survive in extreme environmental conditions. Enzymatic studies of the LDS showed the ability of this fungus to overproduce high amounts of laccase (LACp) in presence of wheat bran or lignin peroxidase (LIPp) with EHCO as sole carbon and energy source (1300 U mgP−1 in both cases). FT-IR spectroscopy with Attenuated Total Reflectance (ATR) analysis showed the enzymatic oxidation of carbon and sulfur atoms in both maltenes and asphaltenes fractions of biotreated EHCO catalysed by cell-free laccase-enriched OE using wheat bran as inducer. UV-visible spectrophotometry analysis revealed the oxidation of the petroporphyrins in the asphaltenes fraction of biotreated EHCO. Tolerance assays showed the ability of this fungus to grow up to 50 000 p.p.m. of EHCO and 2000 mM of NaCl. These results suggest that P. palmarum BM-04 is a hopeful alternative to be used in remediation processes in extreme environmental conditions of salinity and EHCO contamination, such as the drilling waste from the OOB. 相似文献
995.
Joanna M. Poczobutt Miguel Gijon Jay Amin Dwight Hanson Howard Li Deandra Walker Mary Weiser-Evans Xian Lu Robert C. Murphy Raphael A. Nemenoff 《PloS one》2013,8(11)
Eicosanoids are bioactive lipid mediators derived from arachidonic acid1 (AA), which is released by cytosolic phospholipase A2 (cPLA2). AA is metabolized through three major pathways, cyclooxygenase (COX), lipoxygenase (LO) and cytochrome P450, to produce a family of eicosanoids, which individually have been shown to have pro- or anti-tumorigenic activities in cancer. However, cancer progression likely depends on complex changes in multiple eicosanoids produced by cancer cells and by tumor microenvironment and a systematic examination of the spectrum of eicosanoids in cancer has not been performed. We used liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) to quantitate eicosanoids produced during lung tumor progression in an orthotopic immunocompetent mouse model of lung cancer, in which Lewis lung carcinoma (LLC) cells are injected into lungs of syngeneic mice. The presence of tumor increased products of both the cyclooxygenase and the lipoxygenase pathways in a time-dependent fashion. Comparing tumors grown in cPLA2 knockout vs wild-type mice, we demonstrated that prostaglandins (PGE2, PGD2 and PGF2a) were produced by both cancer cells and the tumor microenvironment (TME), but leukotriene (LTB4, LTC4, LTD4, LTE4) production required cPLA2 expression in the TME. Using flow cytometry, we recovered tumor-associated neutrophils and 2 types of tumor-associated macrophages from tumor-bearing lungs and we defined their distinct eicosanoid profiles by LC/MS/MS. The combination of flow cytometry and LC/MS/MS unravels the complexity of eicosanoid production in lung cancer and provides a rationale to develop therapeutic strategies that target select cell populations to inhibit specific classes of eicosanoids. 相似文献
996.
Na‐Ion Batteries for Large Scale Applications: A Review on Anode Materials and Solid Electrolyte Interphase Formation 下载免费PDF全文
Miguel Ángel Muñoz‐Márquez Damien Saurel Juan Luis Gómez‐Cámer Montse Casas‐Cabanas Teófilo Rojo 《Liver Transplantation》2017,7(20)
The urgent need for optimizing the available energy through smart grids and efficient large‐scale energy storage systems is pushing the construction and deployment of Li‐ion batteries in the MW range which, in the long term, are expected to hit the GW dimension while demanding over 1000 ton of positive active material per system. This amount of Li‐based material is equivalent to almost 1% of current Li consumption and can strongly influence the evolution of the lithium supply and cost. Given this uncertainty, it becomes mandatory to develop an energy storage technology that depends on almost infinite and widespread resources: Na‐ion batteries are the best technology for large‐scale applications. With small working cells in the market that cannot compete in cost ($/W h) with commercial Li‐ion batteries, the consolidation of Na‐ion batteries mainly depends on increasing their energy density and stability, the negative electrodes being at the heart of these two requirements. Promising Na‐based negative electrodes for large‐scale battery applications are reviewed, along with the study of the solid electrolyte interphase formed in the anode surface, which is at the origin of most of the stability problems. 相似文献
997.
Regulation of enzymes involved in C4 photosynthesis and the antioxidant metabolism by UV-B radiation in Egeria densa,a submersed aquatic species 总被引:2,自引:0,他引:2
Egeria densa, a submersed aquatic species, was exposed to different treatments under UV-B radiation, and the response of phosphoenolpyruvate
carboxylase (PEPC) and NADP-malic enzyme (NADP-ME) was determined. Exposure to UV-B radiation for 4 h per day over 7–16 days
caused an increase in both enzymes, together with an increase in the activity of some isoforms of several enzymes involved
in the antioxidant metabolism, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and peroxidase
(POD). The content of chlorophylls and carotenoids was considerably decreased, suggesting that degradation or repression of
the synthesis of these molecules may be occurring after UV-B exposure. Reactive oxygen species (ROS) were also required for
UV-B induction of PEPC and NADP-ME, as the addition of ascorbic acid before UV-B treatment prevented the induction of these
enzymes, while salicylic acid was not effective in inducing NADP-ME but increased the expression of the lower molecular mass
isoform of PEPC. On the other hand, damage to the photosynthetic machinery may be occurring after exposure to UV-B radiation
for 8 per day over 1–2 days, as indicated by a decrease in the levels of Rubisco, PEPC and NADP-ME. Some of the enzymes involved
in the antioxidant metabolism, such as CAT and APX, were also sensitive to continuous exposure, evidenced by a decrease in
their activity. In this way, in E. densa, several enzymes involved in different metabolic pathways showed a distinct response, depending on the UV-B treatment.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
998.
999.
Aurora Arrúe Ricardo Dávila Mercedes Zumárraga Nieves Basterreche Miguel A. González-Torres Biotza Goienetxea Maria I. Zamalloa Juan B. Anguiano José Guimón 《Neurochemical research》2010,35(2):247-253
We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic
acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area
with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic
patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared
to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the
controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations
within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA
interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research. 相似文献
1000.
José C. Aponte Abraham J. Vaisberg Denis Castillo German Gonzalez Yannick Estevez Jorge Arevalo Miguel Quiliano Mirko Zimic Manuela Verástegui Edith Málaga Robert H. Gilman Juan M. Bustamante Rick L. Tarleton Yuehong Wang Scott G. Franzblau Guido F. Pauli Michel Sauvain Gerald B. Hammond 《Bioorganic & medicinal chemistry》2010,18(8):2880-2886
The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug-optimization and drug-development efforts for use as therapeutic agents in developing countries. 相似文献