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101.
Kinetic and enzymatic features of metabolic stimulation of alveolar and peritoneal macrophages challenged with bacteria 总被引:3,自引:0,他引:3
The rate of oxygen uptake and of 14C-1-glucose oxidation by peritoneal and alveolar macrophages has been simultaneously recorded before and after the exposure of the cells to B. mycoides. A stimulation of both processes was detected within seconds after the addition of bacteria. A comparison of 14C-1-glucose with 14C-6-glucose oxidation has indicated that the stimulation of the 14CO2 production from 14C-1-glucose is substantially to be ascribed to an increased activity of the HMP pathway. On approaching anaerobiosis, the rate of the HMP pathway fell to zero, showing a direct link between cell respiration and production of NADP+ for the pathway. The assay of an enzyme, catalysing the reaction: NADPH + H+ + O2 → NADP+ + H2O2, in 20 000 g pellets has shown that this oxidase has a higher activity in subcellular fractions derived from macrophages previously exposed to bacteria. The activation of this enzyme may be the most important event in the metabolic stimulation of macrophages challenged with bacteria. On the basis of experiments carried out with KCN, an inhibitor of both NADPH oxidase and catalase, it has been concluded that, under particular conditions, also the concerted action of GSH peroxidase and GSSG reductase might contribute to supporting the HMP pathway activity. 相似文献
102.
J Romeo V Pinphanichakarn Y Iwamoto K Folkers 《Biochemical and biophysical research communications》1974,59(4):1286-1291
Many investigators have purified an aldehyde oxidase from mammalian livers, and described reactions of this enzyme with diverse substrates. Coenzyme Q10 was unambiguously identified and found present in some of these enzyme preparations. It was considered that coenzyme Q10 might participate in the functionality of this enzyme, but the validity of the intrinsic association of coenzyme Q10 was questioned. We have similarly purified aldehyde oxidase from rabbit livers. No coenzyme Q10 could be detected under controlled conditions for detecting the presence of coenzyme Q10. It is concluded that coenzyme Q10 may be a contaminant of some aldehyde oxidase preparations, and that it is not intrinsic for the functionality of this enzyme. 相似文献
103.
Anna Sannino PhD Stefania Romeo PhD Maria Rosaria Scarfì Daniele Pinchera PhD Fulvio Schettino PhD Mario Alonzo PhD Mariateresa Allocca PhD Olga Zeni PhD 《Bioelectromagnetics》2024,45(3):97-109
This study aims to investigate the cellular effects of radiofrequency exposure, 1950 MHz, long-term evolution (LTE) signal, administered alone and in combination with mitomycin-C (MMC), a well-known cytotoxic agent. Chinese hamster lung fibroblast (V79) cells were exposed/sham exposed in a waveguide-based system under strictly controlled conditions of both electromagnetic and environmental parameters, at specific absorption rate (SAR) of 0.3 and 1.25 W/kg. Chromosomal damage (micronuclei formation), oxidative stress (reactive oxygen species [ROS] formation), and cell cycle progression were analyzed after exposure and coexposure. No differences between exposed samples and sham-controls were detected following radiofrequency exposure alone, for all the experimental conditions tested and biological endpoints investigated. When radiofrequency exposure was followed by MMC treatment, 3 h pre-exposure did not modify MMC-induced micronuclei. Pre-exposure of 20 h at 0.3 W/kg did not modify the number of micronuclei induced by MMC, while 1.25 W/kg resulted in a significant reduction of MMC-induced damage. Absence of effects was also detected when CW was used, at both SAR levels. MMC-induced ROS formation resulted significantly decreased at both SAR levels investigated, while cell proliferation and cell cycle progression were not affected by coexposures. The results here reported provide no evidence of direct effects of 1950 MHz, LTE signal. Moreover, they further support our previous findings on the capability of radiofrequency pre-exposure to induce protection from a subsequent toxic treatment, and the key role of the modulated signals and the experimental conditions adopted in eliciting the effect. 相似文献
104.
105.
Elfamycins are a relatively understudied group of antibiotics that target the essential process of translation through impairment of EF‐Tu function. For the most part, the utility of these compounds has been as laboratory tools for the study of EF‐Tu and the ribosome, as their poor pharmacokinetic profile and solubility has prevented implementation as therapeutic agents. However, due to the slowing of the antibiotic pipeline and the rapid emergence of resistance to approved antibiotics, this group is being reconsidered. Some researchers are using screens for novel naturally produced variants, while others are making directed, systematic chemical improvements on publically disclosed compounds. As an example of the latter approach, a GE2270 A derivative, LFF571, has completed phase 2 clinical trials, thus demonstrating the potential for elfamycins to become more prominent antibiotics in the future. 相似文献
106.
107.
Tabrizi MA Baraldi PG Preti D Romagnoli R Saponaro G Baraldi S Moorman AR Zaid AN Varani K Borea PA 《Bioorganic & medicinal chemistry》2008,16(5):2419-2430
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein. 相似文献
108.
Elke De Vuyst Nan Wang Elke Decrock Marijke De Bock Mathieu Vinken Marijke Van Moorhem Charles Lai Maxime Culot Vera Rogiers Romeo Cecchelli Christian C. Naus W. Howard Evans Luc Leybaert 《Cell calcium》2009,46(3):176-187
Connexin hemichannels have a low open probability under normal conditions but open in response to various stimuli, forming a release pathway for small paracrine messengers. We investigated hemichannel-mediated ATP responses triggered by changes of intracellular Ca2+ ([Ca2+]i) in Cx43 expressing glioma cells and primary glial cells. The involvement of hemichannels was confirmed with gja1 gene-silencing and exclusion of other release mechanisms. Hemichannel responses were triggered when [Ca2+]i was in the 500 nM range but the responses disappeared with larger [Ca2+]i transients. Ca2+-triggered responses induced by A23187 and glutamate activated a signaling cascade that involved calmodulin (CaM), CaM-dependent kinase II, p38 mitogen activated kinase, phospholipase A2, arachidonic acid (AA), lipoxygenases, cyclo-oxygenases, reactive oxygen species, nitric oxide and depolarization. Hemichannel responses were also triggered by activation of CaM with a Ca2+-like peptide or exogenous application of AA, and the cascade was furthermore operational in primary glial cells isolated from rat cortex. In addition, several positive feed-back loops contributed to amplify the responses. We conclude that an elevation of [Ca2+]i triggers hemichannel opening, not by a direct action of Ca2+ on hemichannels but via multiple intermediate signaling steps that are adjoined by distinct signaling mechanisms activated by high [Ca2+]i and acting to restrain cellular ATP loss. 相似文献
109.
We investigated the variation of Antarctic fur seal (Arctocephalus gazella) pup growth rates in response to sex, breeding season and duration of both maternal foraging trip and attendance bouts. Data
were collected during five consecutive rearing seasons at Cape Shirreff, the most important breeding colony in the South Shetland
Islands, Antarctica. Our results showed significant interannual and sexual variations in pup growth rates. Male pups grew
significantly faster than female pups during 2000, 2001, 2002 and 2004 seasons, whilst during 2003 no difference was found.
The interannual variation in pup growth rates was correlated with the interannual fluctuation in maternal foraging trip and
attendance bouts. There was a significant effect of pup sex and maternal foraging trip duration on pup growth rates, which
varied between years having foraging trip duration a major effect during 2003, when females spent more time at sea and interestingly
on that year there were no sexual differences in pup growth rates. The effect of attendance bout on pup growth rates was not
significant. Diet analysis showed that Antarctic krill (Euphausia superba) was the most frequent prey item during the study period. Analysis of krill size distribution showed a significant difference
in krill length, during 2003, when A. gazella preyed upon the smallest sizes of krill. In this study, sex was the most important factor on pup growth rates, but when prey
availability seemed more limited, there are longer foraging trips and shorter attendance bouts the sex factor became less
significant. 相似文献
110.
Guobao Zhang Pingda Ren Nathanael S. Gray Taebo Sim Xia Wang Yi Liu Jianwei Che Weitong Dong Shin-Shay Tian Mark L. Sandberg Tracy A. Spalding Russell Romeo Maya Iskandar Zhiliang Wang H. Martin Seidel Donald S. Karanewsky Yun He 《Bioorganic & medicinal chemistry letters》2009,19(23):6691-6695
A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs. 相似文献