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81.
Cleida?A?Oliveira Rong?Nie Kay?Carnes Luiz?R?Franca Gail?S?Prins Philippa?TK?Saunders Rex?A?HessEmail author 《Reproductive biology and endocrinology : RB&E》2003,1(1):75
Background
The antiestrogen ICI 182,780 has been used successfully as an alternative experimental model for the study of estrogen action in the rodent adult male reproductive tract. Although ICI 182,780 causes severe alterations in testicular and efferent ductule morphology and function, the effects on the expression of estrogen and androgen receptors in the male have not been shown. 相似文献82.
Forty-eight hours after unilateral nephrectomy in young male Sprague-Dawley rats the concentrations of free methionine, alanine and tyrosine in renal cortical tissue were increased by 15-65 percent while the corresponding plasma concentrations decreased by 23-35 percent. The renal cortical concentrations of valine and leucine increased by 41 percent and 26 percent while plasma concentrations remained unchanged. The cortical concentrations of ornithine, serine and threonine remained unchanged while the plasma concentration decreased by approximately one-third. The total free amino acid contained in the cortex was not changed, while total free amino acids in plasma decreased by 7 percent. These data are thought to reflect an increased uptake of methionine and tyrosine into renal cells during compensatory hypertrophy, and an increased incorporation into renal protein of serine, threonine and ornithine. All these changes as well as all other biochemical changes accompanying compensatory hypertrophy with the exception of an increase of the RNA/DNA ratio were prevented by starvation for 48 hours after unilateral nephrectomy.In young male Sprague-Dawley rats and adult male Charles River mice, the incorporation of 14C-choline into acid-insoluble phospholipids (phosphatidylcholine, lysophosphatidylcholine and sphingomyelin) was already accelerated 5 minutes after contralateral nephrectomy and further rose to +68 ± 7 percent within 20 minutes to 3 hours. Incorporation of 14C-choline into phospholipids remained accelerated for two to three days and reflected increased rates of phospholipid synthesis rather than increased choline uptake. Three hours after unilateral nephrectomy in mice, incorporation of i.p. injected 14C-choline into phospholipids was accelerated 25 percent. The rate of turnover of free labelled renal phospholipids was not accelerated during compensatory renal growth. The very early increase of choline incorporation into phospholipids after contralateral nephrectomy, therefore, appears to reflect an increased rate of synthesis of membrane material. 相似文献
83.
Radial diffusion of enzymes into a casein-containing gel is a fast and inexpensive technique for determination of proteolytic enzymes. A simple method for the preparation of substrate plates with a homogeneous distribution of caseinate and buffered at selected pH values between 2.8 and 4.8 has been described in this communication. By determination of pepsin in caseinate gels the accuracy was better than that described for photometric pepsin assays, and the sensitivity was 300 times greater. 相似文献
84.
Huang Y Man HY Sekine-Aizawa Y Han Y Juluri K Luo H Cheah J Lowenstein C Huganir RL Snyder SH 《Neuron》2005,46(4):533-540
Postsynaptic AMPA receptor (AMPAR) trafficking mediates some forms of synaptic plasticity that are modulated by NMDA receptor (NMDAR) activation and N-ethylmaleimide sensitive factor (NSF). We report that NSF is physiologically S-nitrosylated by endogenous, neuronally derived nitric oxide (NO). S-nitrosylation of NSF augments its binding to the AMPAR GluR2 subunit. Surface insertion of GluR2 in response to activation of synaptic NMDARs requires endogenous NO, acting selectively upon the binding of NSF to GluR2. Thus, AMPAR recycling elicited by NMDA neurotransmission is mediated by a cascade involving NMDA activation of neuronal NO synthase to form NO, leading to S-nitrosylation of NSF which is thereby activated, enabling it to bind to GluR2 and promote the receptor's surface expression. 相似文献
85.
Mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence
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Enhanced mutagenesis may result in RNA virus extinction, but the molecular events underlying this process are not well understood. Here we show that 5-fluorouracil (FU)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (LCMV) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. Furthermore, fitness recovery passages in the absence of FU, or alternate virus passages in the presence and absence of FU, led to profound differences in the capacity of LCMV to produce progeny, without modification of the consensus genomic sequence. Molecular genetic analysis failed to produce evidence of hypermutated LCMV genomes. The results suggest that low-level mutagenesis to enrich the viral population with defector, interfering genomes harboring limited numbers of mutations may mediate the loss of infectivity that accompanies viral extinction. 相似文献
86.
Guillot C Coathalem H Chetritt J David A Lowenstein P Gilbert E Tesson L van Rooijen N Cuturi MC Soulillou JP Anegon I 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(8):5225-5235
The putative role of IL-4 in human and animal models of hepatitis has not yet been directly determined. We now report that direct expression of IL-4 in the liver of rats or mice using recombinant adenoviruses coding for rat or mouse IL-4 (AdrIL-4 and AdmIL-4, respectively) results in a lethal, dose-dependent hepatitis. The hepatitis induced by IL-4 was characterized by hepatocyte apoptosis and a massive monocyte/macrophage infiltrate. IL-4-induced hepatitis was independent of T cell-mediated immune responses. Hepatitis occurred even after gene transfer of IL-4 into nude rats, CD8-depleted rats, cyclosporine A-treated rats, or recombinase-activating gene 2(-/-) immunodeficient mice. Peripheral depletion of leukocytes using high doses of cyclophosphamide, and/or the specific depletion of liver macrophages with liposome-encapsulated dichloromethylene diphosphonate in rats did not block lethal IL-4-induced hepatitis. Direct transduction of hepatocytes with adenoviruses was not essential, since injection of AdrIL-4 into the hind limb induced an identical hepatitis. Finally, primary rat hepatocytes in culture also showed apoptosis when cultured in the presence of rIL-4. IL-4-dependent hepatitis was associated with increases in the intrahepatic levels of IFN-gamma, TNF-alpha, and Fas ligand. Administration of AdmIL-4 to IFN-gamma, TNF-alpha receptor type I, or TNF-alpha receptor type II knockout mice also resulted in lethal hepatitis, whereas a moderate protection was observed in Fas-deficient lpr mice. IL-4-dependent hepatocyte apoptosis could be abolished by treatment with caspase inhibitory peptides. Our results thus demonstrate that IL-4 causes hepatocyte apoptosis, which is only partially dependent on the activation of Apo-1-Fas signaling and is largely independent of any immune cells in the liver. 相似文献
87.
Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo. 总被引:11,自引:0,他引:11
M Ozaki S S Deshpande P Angkeow J Bellan C J Lowenstein M C Dinauer P J Goldschmidt-Clermont K Irani 《FASEB journal》2000,14(2):418-429
Reperfusion of ischemic tissue results in the generation of reactive oxygen species that contribute to tissue injury. The sources of reactive oxygen species in reperfused tissue are not fully characterized. We hypothesized that the small GTPase Rac1 mediates the oxidative burst in reperfused tissue and thereby contributes to reperfusion injury. In an in vivo model of mouse hepatic ischemia/reperfusion injury, recombinant adenoviral expression of a dominant negative Rac1 (Rac1N17) completely suppressed the ischemia/reperfusion-induced production of reactive oxygen species and lipid peroxides, activation of nuclear factor-kappa B, and resulted in a significant reduction of acute liver necrosis. Expression of Rac1N17 also suppressed ischemia/reperfusion-induced acute apoptosis. The protection offered by Rac1N17 was also evident in knockout mice deficient for the gp91phox component of the phagocyte NADPH oxidase. This work demonstrates the crucial role of a Rac1-regulated oxidase in mediating the production of injurious reactive oxygen species, which contribute to acute necrotic and apoptotic cell death induced by ischemia/reperfusion in vivo. Targeted inhibition of this oxidase, which is distinct from the phagocyte NADPH oxidase, should provide a new avenue for in vivo therapy aimed at protecting organs at risk from ischemia/reperfusion injury.-Ozaki, M., Deshpande, S. S., Angkeow, P., Bellan, J., Lowenstein, C. J., Dinauer, M. C., Goldschmidt-Clermont, P. J., Irani, K. Inhibition of the Rac1 GTPase protects against nonlethal ischemia/reperfusion-induced necrosis and apoptosis in vivo. 相似文献
88.
Adenylate deaminase from rat skeletal muscle has been studied with the objective of understanding how the activity of the enzyme is regulated in vivo. ATP and GTP inhibit the enzyme at low concentrations in the presence of 150 mM KCl. The ATP inhibition is reversed as the ATP concentration is raised to physiological levels. The GTP inhibition is reversed as the GTP concentration is raised to unphysiologically high levels. In the presence of physiological concentrations of ATP, the GTP inhibition is also greatly diminished, but inhibition by orthophosphate remains strong. The apparent affinities of the enzyme for GTP, ATP, and orthophosphate are reduced as the pH is decreased from 7.0 to 6.2. ADP also reduces the apparent affinities of the enzyme for the inhibitors. The regulatory effects of GTP, ATP, and ADP are produced primarily by their unchelated forms. Comparison of the kinetic behavior of the enzyme in vitro with metabolite concentrations in vivo indicates that the major variables that regulate the activity of adenylate deaminase of muscle in vivo are the concentrations of AMP, ADP, orthophosphate, and H+. 相似文献
89.
Vascular inflammation plays a key role in the pathogenesis of atherosclerosis. The first step in vascular inflammation is endothelial exocytosis, in which endothelial granules fuse with the plasma membrane, releasing prothrombotic and proinflammatory messenger molecules. The development of cell culture models to study endothelial exocytosis has been challenging because the factors that modulate exocytosis in vitro are not well understood. Here we report a method for studying endothelial exocytosis that optimizes extracellular matrix components, cell density, and duration of culture. Human umbilical vein endothelial cells plated on collagen I-coated plates and cultured in the confluent state for 7–12 days in low-serum medium showed robust secretion of von Willebrand factor when stimulated with various agonists. This exocytosis assay is rapid and applicable to high-throughput screening. 相似文献
90.