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41.
In Drosophila S2 cells, the apical caspase DRONC undergoes a low level of spontaneous autoprocessing. Unintended apoptosis is prevented by the inhibitor of apoptosis DIAP1, which targets the processed form of DRONC for degradation through its E3 ubiquitin protein ligase activity. Recent reports have demonstrated that shortly after the initiation of apoptosis in S2 cells, DIAP1 is cleaved following aspartate residue Asp-20 by the effector caspase DrICE. Here we report a novel caspase-mediated cleavage of DIAP1 in S2 cells. In both living and dying S2 cells, DIAP1 is cleaved by DRONC after glutamate residue Glu-205, located between the first and second BIR domains. The mutation of Glu-205 prevented the interaction of DIAP1 and processed DRONC but had no effect on the interaction with full-length DRONC. The mutation of Glu-205 also had a negative effect on the ability of overexpressed DIAP1 to prevent apoptosis stimulated by the proapoptotic protein Reaper or by UV light. These results expand our knowledge of the events that occur in the Drosophila apoptosome prior to and after receiving an apoptotic signal. 相似文献
42.
Pulse radiolysis has been employed to investigate the intramolecular electron transfer (ET) between the type 1 (T1) and type 2 (T2) copper sites in the Met144Ala Alcaligenes xylosoxidans nitrite reductase (AxCuNiR) mutant. This mutation increases the reduction potential of the T1 copper center. Kinetic results suggest that the change in driving force has a dramatic influence on the reactivity: The T2Cu(II) is initially reduced followed by ET to T1Cu(II). The activation parameters have been determined and are compared with those of the wild-type (WT) AxCuNiR. The reorganization energy of the T2 site in the latter enzyme was calculated to be 1.6+/-0.2 eV which is two-fold larger than that of the T1 copper center in the WT protein. 相似文献
43.
Ohana E Segal D Palty R Ton-That D Moran A Sensi SL Weiss JH Hershfinkel M Sekler I 《The Journal of biological chemistry》2004,279(6):4278-4284
Zinc influx, driven by a steep inward electrochemical gradient, plays a fundamental role in zinc signaling and in pathophysiologies linked to intracellular accumulation of toxic zinc. Yet, the cellular transport mechanisms that actively generate or maintain the transmembrane gradients are not well understood. We monitored Na+-dependent Zn2+ transport in HEK293 cells and cortical neurons, using fluorescent imaging. Treatment of the HEK293 cells with CaPO4 precipitates induced Na+-dependent Zn2+ extrusion, against a 500-fold transmembrane zinc gradient, or zinc influx upon reversal of Na+ gradient, thus indicating that Na+/Zn2+ exchange is catalyzing active Zn2+ transport. Depletion of intracellular ATP did not inhibit the Na+-dependent Zn2+ extrusion, consistent with a mechanism involving a secondary active transporter. Inhibitors of the Na+/Ca2+ exchanger failed to inhibit Na+-dependent Zn2+ efflux. In addition, zinc transport was unchanged in HEK293 cells heterologously expressing functional cardiac or neuronal Na+/Ca2+ exchangers, thus indicating that the Na+/Zn2+ exchange activity is not mediated by the Na+/Ca2+ exchanger. Sodium-dependent zinc exchange, facilitating the removal of intracellular zinc, was also monitored in neurons. To our knowledge, the Na+/Zn2+ exchanger described here is the first example of a mammalian transport mechanism capable of Na+-dependent active extrusion of zinc. Such mechanism is likely to play an important role, not only in generating the transmembrane zinc gradients, but also in protecting cells from the potentially toxic effects of permeation of this ion. 相似文献
44.
Differential role of CCR2 in islet and heart allograft rejection: tissue specificity of chemokine/chemokine receptor function in vivo 总被引:5,自引:0,他引:5
Abdi R Means TK Ito T Smith RN Najafian N Jurewicz M Tchipachvili V Charo I Auchincloss H Sayegh MH Luster AD 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(2):767-775
Chemokines have a pivotal role in the mobilization and activation of specific leukocyte subsets in acute allograft rejection. However, the role of specific chemokines and chemokine receptors in islet allograft rejection has not been fully elucidated. We now show that islet allograft rejection is associated with a steady increase in intragraft expression of the chemokines CCL8 (monocyte chemoattractant protein-2), CCL9 (monocyte chemoattractant protein-5), CCL5 (RANTES), CXCL-10 (IFN-gamma-inducible protein-10), and CXCL9 (monokine induced by IFN-gamma) and their corresponding chemokine receptors CCR2, CCR5, CCR1, and CXCR3. Because CCR2 was found to be highly induced, we tested the specific role of CCR2 in islet allograft rejection by transplanting fully MHC mismatched islets from BALB/c mice into C57BL/6 wild-type (WT) and CCR2-deficient mice (CCR2-/-). A significant prolongation of islet allograft survival was noted in CCR2-/- recipients, with median survival time of 24 and 12 days for CCR2-/- and WT recipients, respectively (p < 0.0001). This was associated with reduction in the generation of CD8+, but not CD4+ effector alloreactive T cells (CD62L(low)CD44(high)) in CCR2-/- compared with WT recipients. In addition, CCR2-/- recipients had a reduced Th1 and increased Th2 alloresponse in the periphery (by ELISPOT analysis) as well as in the grafts (by RT-PCR). However, these changes were only transient in CCR2-/- recipients that ultimately rejected their grafts. Furthermore, in contrast to the islet transplants, CCR2 deficiency offered only marginal prolongation of heart allograft survival. This study demonstrates the important role for CCR2 in early islet allograft rejection and highlights the tissue specificity of the chemokine/chemokine receptor system in vivo in regulating allograft rejection. 相似文献
45.
On the mechanisms of the reaction of dodecatungstophosphate with alkyl radicals in aqueous solutions
Inna Popivker Israel Zilbermann Eric Maimon Yosef Matana Dan Meyerstein 《Inorganica chimica acta》2010,363(15):4202-4206
The reduced lacunary polyoxotungstate, [PW11O39]8−, reacts with the .CH2CH(OH)CH3 and .CH2C(CH3)2OH radicals via a mechanism involving β-hydroxide elimination to yield propene and 2-methyl propene respectively, and [PW11O39]7−. [PW11O39]8− is also oxidized by methyl radicals in a reaction which yields methane as the major product. It is proposed that the reactions proceed via the formation of short lived transients with W-C σ bonds. 相似文献
46.
47.
An increasing amount of evidence indicates that N can be transferred between plants. Nonetheless, a number of fundamental
questions remain. A series of experiments was initiated in the field to examine N transfer between N2-fixing soybean (Glycine max [L.] Merr.) varieties and a non-nodulating soybean, and between N2-fixing peanut (Arachis hypogaea L.) or soybean and neighboring weed species. The experiments were conducted in soils with low N fertilities and used differences
in N accumulation and/or 15N natural abundance to estimate N transfer. Mixtures of N2-fixing and non-nod soybean indicated that substantial inter-plant N transfer occurred. Amounts were variable, ranging from
negligible levels to 48% of the N found in the non-nod at maturity. Transfer did not appear to strongly penalize the N2-fixing donor plants. But, in cases where high amounts of N were transferred, N content of donors was noticeably lowered.
Differences were evident in the amount of N transferred from different N2-fixing donor genotypes. Results of experiments with N2-fixing crops and the weed species prickly sida (Sida spinosa L.) and sicklepod (Senna obtusifolia [L.] Irwin & Barneby) also indicated substantial N transfer occurred over a 60-day period, with amounts accounting for 30–80%
of the N present in the weeds. Transfer of N, however, was generally very low in weed species that are known to be non-hosts
for arbuscular mycorrhizae (yellow nutsedge, Cyperus esculentus L. and Palmer amaranth, Amaranthus palmeri [S.] Watson). The results are consistent with the view that N transfer occurs primarily through mycorrhizal hyphal networks,
and they reveal that N transfer may be a contributing factor to weed problems in N2-fixing crops in low N fertility conditions. 相似文献
48.
Sokalska A Cress A Bruner-Tran KL Osteen KG Taylor HS Ortega I Duleba AJ 《Biology of reproduction》2012,87(1):2, 1-2, 6
Recently we reported that statins, the competitive inhibitors of the key enzyme regulating the mevalonate pathway, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), decrease proliferation of human endometrial stromal (HES) cells. Furthermore, we found that simvastatin treatment reduces the number and the size of endometrial implants in a nude mouse model of endometriosis. The present study was undertaken to investigate the effect of simvastatin on HES cell invasiveness and on expression of selected genes relevant to invasiveness: matrix metalloproteinase 2 (MMP2), MMP3, tissue inhibitor of matrix metalloproteinase 2 (TIMP2), and CD44. Because statin-induced inhibition of HMGCR reduces the production of substrates for isoprenylation-geranylgeranyl pyrophosphate (GGPP) and farnesyl pyrophosphate (FPP)-the effects of GGPP and FPP were also evaluated. Simvastatin induced a concentration-dependent reduction of invasiveness of HES cells. This effect of simvastatin was abrogated by GGPP but not by FPP. Simvastatin also reduced the mRNA levels of MMP2, MMP3, and CD44, but increased TIMP2 mRNA; all these effects of simvastatin were partly or entirely reversed in the presence of GGPP. The present findings provide a novel mechanism of action of simvastatin on endometrial stroma that may explain reduction of endometriosis in animal models of this disease. Furthermore, the presently described effects of simvastatin are likely mediated, at least in part, by inhibition of geranylgeranylation. 相似文献
49.
Morvan D Steyaert JM Schwartz L Israel M Demidem A 《American journal of physiology. Endocrinology and metabolism》2012,302(11):E1407-E1418
50.
Estefanía Custodio Endalamaw Gadisa Luis Sordo Israel Cruz Javier Moreno Javier Nieto Carmen Chicharro Abraham Aseffa Zelalem Abraham Tsegaye Hailu Carmen Ca?avate 《PLoS neglected tropical diseases》2012,6(9)