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991.
Alejandro Lopez-Tobón Efraín Cepeda-Prado Gloria Patricia Cardona-Gómez 《Neurochemical research》2009,34(12):2206-2214
Several studies have linked estrogens with sphingosine kinase (SphK) activity, enzyme responsible of sphingosine-1-phosphate
synthesis (S-1P), however their possible interaction in the nervous system is not documented yet. In the present study, we
developed a glutamate toxicity model in SH-SY5Y cells to evaluate the possible effect of the inhibition of SphK activity on
the protective capability of 17β-estradiol (E2). Glutamate induced cytoskeletal actin changes associated to cytotoxic stress,
significant increase of apoptotic-like nuclear fragmentation, Tau hyperphosphorylation and increase of p25/p35 cleavage. These
effects were prevented by E2 pre-treatment during 24 h. Although the inhibition of SphK did not block this protective effect,
significantly increased Tau hyperphosphorylation by glutamate, in a way that was not reverted by E2. Our results suggest that
the decrease of glutamate-induced Tau hyperphosphorylation by 17β-estradiol requires SphK. 相似文献
992.
Ramirez DC Gomez-Mejiba SE Corbett JT Deterding LJ Tomer KB Mason RP 《The Biochemical journal》2009,417(1):341-353
The understanding of the mechanism, oxidant(s) involved and how and what protein radicals are produced during the reaction of wild-type SOD1 (Cu,Zn-superoxide dismutase) with H2O2 and their fate is incomplete, but a better understanding of the role of this reaction is needed. We have used immuno-spin trapping and MS analysis to study the protein oxidations driven by human (h) and bovine (b) SOD1 when reacting with H2O2 using HSA (human serum albumin) and mBH (mouse brain homogenate) as target models. In order to gain mechanistic information about this reaction, we considered both copper- and CO3(*-) (carbonate radical anion)-initiated protein oxidation. We chose experimental conditions that clearly separated SOD1-driven oxidation via CO(*-) from that initiated by copper released from the SOD1 active site. In the absence of (bi)carbonate, site-specific radical-mediated fragmentation is produced by SOD1 active-site copper. In the presence of (bi)carbonate and DTPA (diethylenetriaminepenta-acetic acid) (to suppress copper chemistry), CO(*-) produced distinct radical sites in both SOD1 and HSA, which caused protein aggregation without causing protein fragmentation. The CO(*-) produced by the reaction of hSOD1 with H2O2 also produced distinctive DMPO (5,5-dimethylpyrroline-N-oxide) nitrone adduct-positive protein bands in the mBH. Finally, we propose a biochemical mechanism to explain CO(*-) production from CO2, enhanced protein radical formation and protection by (bi)carbonate against H2O2-induced fragmentation of the SOD1 active site. Our present study is important for establishing experimental conditions for studying the molecular mechanism and targets of oxidation during the reverse reaction of SOD1 with H2O2; these results are the first step in analysing the critical targets of SOD1-driven oxidation during pathological processes such as neuroinflammation. 相似文献
993.
Arturo Andrade Alejandro Sandoval Ricardo Gonzlez-Ramírez Diane Lipscombe Kevin P. Campbell Ricardo Felix 《Cell calcium》2009,46(4):282-292
The auxiliary CaVα2δ-1 subunit is an important component of voltage-gated Ca2+ (CaV) channel complexes in many tissues and of great interest as a drug target. Nevertheless, its exact role in specific cell functions is still unknown. This is particularly important in the case of the neuronal L-type CaV channels where these proteins play a key role in the secretion of neurotransmitters and hormones, gene expression, and the activation of other ion channels. Therefore, using a combined approach of patch-clamp recordings and molecular biology, we studied the role of the CaVα2δ-1 subunit on the functional expression and the pharmacology of recombinant L-type CaV1.3 channels in HEK-293 cells. Co-expression of CaVα2δ-1 significantly increased macroscopic currents and conferred the CaV1.3α1/CaVβ3 channels sensitivity to the antiepileptic/analgesic drugs gabapentin and AdGABA. In contrast, CaVα2δ-1 subunits harboring point mutations in N-glycosylation consensus sequences or the proteolytic site as well as in conserved cysteines in the transmembrane δ domain of the protein, reduced functionality in terms of enhancement of CaV1.3α1/CaVβ3 currents. In addition, co-expression of the δ domain drastically inhibited macroscopic currents through recombinant CaV1.3 channels possibly by affecting channel synthesis. Together these results provide several lines of evidence that the CaVα2δ-1 auxiliary subunit may interact with CaV1.3 channels and regulate their functional expression. 相似文献
994.
Two anion transporters AtClCa and AtClCe fulfil interconnecting but not redundant roles in nitrate assimilation pathways 总被引:1,自引:0,他引:1
995.
Dario C. Altieri Lucia R. Languino Jane B. Lian Janet L. Stein Irwin Leav Andre J. van Wijnen Zhong Jiang Gary S. Stein 《Journal of cellular biochemistry》2009,107(5):845-852
Although the timing with which common epithelial malignancies arise and become established remains a matter of debate, it is clear that by the time they are detected these tumors harbor hundreds of deregulated, aberrantly expressed or mutated genes. This enormous complexity poses formidable challenges to identify gene pathways that are drivers of tumorigenesis, potentially suitable for therapeutic intervention. An alternative approach is to consider cancer pathways as interconnected networks, and search for potential nodal proteins capable of connecting multiple signaling networks of tumor maintenance. We have modeled this approach in advanced prostate cancer, a condition with current limited therapeutic options. We propose that the integration of three signaling networks, including chaperone‐mediated mitochondrial homeostasis, integrin‐dependent cell signaling, and Runx2‐regulated gene expression in the metastatic bone microenvironment plays a critical role in prostate cancer maintenance, and offers novel options for molecular therapy. J. Cell. Biochem. 107: 845–852, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
996.
Sandra E. Gomez-Mejiba Zili Zhai Hammad Akram Leesa J. Deterding Kenneth Hensley Nataliya Smith Rheal A. Towner Kenneth B. Tomer Ronald P. Mason Dario C. Ramirez 《Free radical biology & medicine》2009,46(7):853-865
Biomolecule-centered radicals are intermediate species produced during both reversible (redox modulation) and irreversible (oxidative stress) oxidative modification of biomolecules. These oxidative processes must be studied in situ and in real time to understand the molecular mechanism of cell adaptation or death in response to changes in the extracellular environment. In this regard, we have developed and validated immuno-spin trapping to tag the redox process, tracing the oxidatively generated modification of biomolecules, in situ and in real time, by detecting protein- and DNA-centered radicals. The purpose of this methods article is to introduce and update the basic methods and applications of immuno-spin trapping for the study of redox biochemistry in oxidative stress and redox regulation. We describe in detail the production, detection, and location of protein and DNA radicals in biochemical systems, cells, and tissues, and in the whole animal as well, by using immuno-spin trapping with the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide. 相似文献
997.
Alejandro G. Farji-Brener Ernesto Gianoli Marco A. Molina-Montenegro 《Ecological Research》2009,24(1):139-145
Small-scale disturbances caused by animals often modify soil resource availability and may also affect plant attributes. Changes
in the phenotype of plants growing on disturbed, nutrient-enriched microsites may influence the distribution and abundance
of associated insects. We evaluated how the high nutrient availability generated by leaf-cutting ant nests in a Patagonian
desert steppe may spread along the trophic chain, affecting the phenotype of two thistle species, the abundance of a specialist
aphid and the composition of the associated assemblage of tending ants. Plants of the thistle species Carduus nutans and Onopordum acanthium growing in piles of waste material generated by leaf-cutting ant nests (i.e., refuse dumps) had more leaves, inflorescences
and higher foliar nitrogen content than those in non-nest soils. Overall, plants in refuse dumps showed higher abundance of
aphids than plants in non-nest soils, and aphid colonies were of greater size on O. acanthium plants than on C. nutans plants. However, only C. nutans plants showed an increase in aphid abundance when growing on refuse dumps. This resulted in a similar aphid load in both
thistle species when growing on refuse dumps. Accordingly, only C. nutans showed an increase in the number of ant species attending aphids when growing on refuse dumps. The increase of soil fertility
generated by leaf-cutting ant nests can affect aphid abundance and their tending ant assemblage through its effect on plant
size and quality. However, the propagation of small-scale soil disturbances through the trophic chain may depend on the identity
of the species involved. 相似文献
998.
999.
João Neres Mark L. Brewer Laura Ratier Horacio Botti Alejandro Buschiazzo Philip N. Edwards Paul N. Mortenson Michael H. Charlton Pedro M. Alzari Alberto C. Frasch Richard A. Bryce Kenneth T. Douglas 《Bioorganic & medicinal chemistry letters》2009,19(3):589-596
trans-Sialidase from Trypanosoma cruzi (TcTS) has emerged as a potential drug target for treatment of Chagas disease. Here, we report the results of virtual screening for the discovery of novel TcTS inhibitors, which targeted both the sialic acid and sialic acid acceptor sites of this enzyme. A library prepared from the Evotec database of commercially available compounds was screened using the molecular docking program GOLD, following the application of drug-likeness filters. Twenty-three compounds selected from the top-scoring ligands were purchased and assayed using a fluorimetric assay. Novel inhibitor scaffolds, with IC50 values in the submillimolar range were discovered. The 3-benzothiazol-2-yl-4-phenyl-but-3-enoic acid scaffold was studied in more detail, and TcTS inhibition was confirmed by an alternative sialic acid transfer assay. Attempts to obtain crystal structures of these compounds with TcTS proved unsuccessful but provided evidence of ligand binding at the active site. 相似文献
1000.
Antonio G. Checa Francisco J. Esteban-Delgado Joaquín Ramírez-Rico Alejandro B. Rodríguez-Navarro 《Journal of structural biology》2009,167(3):261-270
The calcitic columnar prisms of pteriomorphian bivalves have the crystallographic c-axis oriented perpendicular to the shell surface and the a-axes rotated without any preferential orientation. In oysters, SEM, XRD and EBSD analyses show that individual prisms initially have their a-axes randomly oriented but are able to progressively orient them parallel to those of their neighbors. This ability is apparently confined to groups, such as oysters and scallops, in which prisms are internally constituted by smaller lath-like crystal units. We have developed a competition model – not between prisms, but between the lath-like secondary units of prisms – which is based on differences in the inclination of laths relative to the shell growth surface. Units having a growth component which coincides with the growth direction protrude faster from the growth surface and out-compete those which are not favorably oriented, which reduces the overall dispersion of the a-axes of the prismatic lamella. The extent of re-alignment increases with the relative inclination of the growth surface and the length attained by the prisms. Oysters are the only group in which these two characters are pronounced enough to provide a measurable re-alignment. The proposed competition model is unprecedented in biomaterials and reveals how important crystal growth processes are in microstructure organization. 相似文献