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Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity 总被引:1,自引:0,他引:1
Valet P Grujic D Wade J Ito M Zingaretti MC Soloveva V Ross SR Graves RA Cinti S Lafontan M Lowell BB 《The Journal of biological chemistry》2000,275(44):34797-34802
Catecholamines play an important role in controlling white adipose tissue function and development. beta- and alpha 2-adrenergic receptors (ARs) couple positively and negatively, respectively, to adenylyl cyclase and are co-expressed in human adipocytes. Previous studies have demonstrated increased adipocyte alpha 2/beta-AR balance in obesity, and it has been proposed that increased alpha 2-ARs in adipose tissue with or without decreased beta-ARs may contribute mechanistically to the development of increased fat mass. To critically test this hypothesis, adipocyte alpha 2/beta-AR balance was genetically manipulated in mice. Human alpha 2A-ARs were transgenically expressed in the adipose tissue of mice that were either homozygous (-/-) or heterozygous (+/-) for a disrupted beta 3-AR allele. Mice expressing alpha 2-ARs in fat, in the absence of beta 3-ARs (beta 3-AR -/- background), developed high fat diet-induced obesity. Strikingly, this effect was due entirely to adipocyte hyperplasia and required the presence of alpha2-ARs, the absence of beta 3-ARs, and a high fat diet. Of note, obese alpha 2-transgenic beta 3 -/- mice failed to develop insulin resistance, which may reflect the fact that expanded fat mass was due to adipocyte hyperplasia and not adipocyte hypertrophy. In summary, we have demonstrated that increased alpha 2/beta-AR balance in adipocytes promotes obesity by stimulating adipocyte hyperplasia. This study also demonstrates one way in which two genes (alpha 2 and beta 3-AR) and diet interact to influence fat mass. 相似文献
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A. K. Martusevich S. P. Peretyagin A. G. Soloveva A. A. Martusevich A. D. Plekhanova 《Biophysics》2016,61(1):139-143
The goal of this work was to study the influence of nitric oxide inhalation on parameters of blood proand antioxidant systems in rats under both an intact condition and experimental thermal injury. We studied 40 Wistar rats that were divided into four equal groups. The intact group was subjected to no manipulation exñept a single blood sampling, main group I was subjected to inhalation of a air mixture containing 20 ppm of nitric oxide for 10 days, the control group was subjected to thermal injury and conventional treatment, and main group II was subjected to thermal injury and daily inhalation of nitric oxide (20 ppm) for 10 days. We studied the intensity of lipid peroxidation in the blood plasma, the total antioxidant activity, the peroxide resistance of erythrocytes, the level of malondialdehyde in the blood plasma and erythrocytes, and the activity of superoxide dismutase. It was shown that daily inhalations of a mixture containing a low concentration of nitric oxide (20 ppm) modified blood oxidative metabolism in healthy and burned rats. We hypothesized that the activation of lipid peroxidation in erythrocytes accompanied by a pronounced increase in the catalytic activity of superoxide dismutase is a unified response of healthy and burned rats to exogenous nitric oxide exposure. We also observed a moderate prooxidant effect in the blood plasma of healthy animals comparable to that in the erythrocytes of these rats. In the case of thermal injury, oxidative stress tended to be corrected after the end of the course of inhalation. 相似文献
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Soloveva I. V. Novikova N. A. Tochilina A. G. Belova I. V. Kashnikov A. Yu. Sashina T. A. Zhirnov V. A. Molodtsova S. B. 《Microbiology》2021,90(2):219-225
Microbiology - Lactobacillus fermentum 39 is a well-known probiotic strain, which is widely used for production of pharmacopoeial probiotic preparations, dietary supplements, and foodstuffs... 相似文献
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This paper presents the results of the study of oxidative metabolism of the blood of intact animals subjected to prolonged exposure to nitric oxide at concentrations of 20, 50, and 100 ppm. The experiment was carried out with Wistar rats. NO inhalation was performed for 30 days. The state of blood oxidative metabolism was evaluated after inhalation and a 30-day-long recovery period after discontinuation of NO oxidative stress. The intensity of lipid peroxidation was studied in plasma and erythrocytes by induced biochemiluminescence and the measurement of the level of malondialdehyde. The activity of superoxide dismutase was determined in the hemolysate of erythrocytes. It was established that the optimal dose of inhaled NO is 20 ppm: a maximum increase in the total antioxidant activity after 30 days and normalization of lipid peroxidation in the blood after the completion of the recovery period were observed at this concentration. High concentrations of nitric oxide (50 and 100 ppm) initiated lipid peroxidation in erythrocytes and plasma after discontinuation of NO oxidative stress (after the completion of the recovery period) thus enhancing catalytic properties of superoxide dismutase. 相似文献
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Krishna P. Kota Veronica Soloveva Laura M. Wanner Glenn Gomba Erkan Kiris Rekha G. Panchal Christopher D. Kane Sina Bavari 《Journal of visualized experiments : JoVE》2014,(93)
Synaptosomal-associated protein-25 (SNAP-25) is a component of the soluble NSF attachment protein receptor (SNARE) complex that is essential for synaptic neurotransmitter release. Botulinum neurotoxin serotype A (BoNT/A) is a zinc metalloprotease that blocks exocytosis of neurotransmitter by cleaving the SNAP-25 component of the SNARE complex. Currently there are no licensed medicines to treat BoNT/A poisoning after internalization of the toxin by motor neurons. The development of effective therapeutic measures to counter BoNT/A intoxication has been limited, due in part to the lack of robust high-throughput assays for screening small molecule libraries. Here we describe a high content imaging (HCI) assay with utility for identification of BoNT/A inhibitors. Initial optimization efforts focused on improving the reproducibility of inter-plate results across multiple, independent experiments. Automation of immunostaining, image acquisition, and image analysis were found to increase assay consistency and minimize variability while enabling the multiparameter evaluation of experimental compounds in a murine motor neuron system. 相似文献
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The influence of electromagnetic radiation of extremely high frequencies in the noise mode on the level of the activity of proand antioxidant systems in a model of skin-flap ischemia was studied in vivo. Rats of the Wistar line were used in this work. The cutaneous reflex projection field of the animals was exposed once a day for 7 days in the post-operative period to electromagnetic radiation of an extremely high frequency in the range from 53.57 to 78.33 GHz with a dose of 1.2 mJ in the noise mode. The dynamics of proand antioxidant protection were compared to those of intact animals that were not irradiated. Using data on induced biochemiluminescence and estimation of malondialdehyde activity it was shown that irradiation in a course mode contributed to a decrease in the intensity of lipid peroxidation. In parallel we observed an increase in the total antioxidant reserves of blood and the activity of bioradical protection enzymes. Our findings suggest that electromagnetic radiation at extremely high frequencies in a noise mode has a regulatory impact on the state of proand antioxidant systems of the body; this can be used for the correction of postoperative ischemic disorders and the restoration of disturbed homeostasis. 相似文献
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Elena Lipets Olga Vlasova Evdokiya Urnova Oleg Margolin Anna Soloveva Olga Ostapushchenko John Andersen Fazoil Ataullakhanov Mikhail Panteleev 《PloS one》2014,9(1)
Background and Objective
Using an in vitro experimental model of immobilized tissue factor-initiated clot growth in platelet-free plasma (thrombodynamics), we observed formation of activator-independent isolated spontaneous clots (SC) throughout the plasma volume in patients with cardiac infarction, acute leukemia, hemolytic anemia, and some other disorders. The aim of this work was to characterize this phenomenon and to identify the mechanisms of SC formation.Methods and Results
Tissue factor inhibitor (VIIai) prevented SC in only 2 out of 23 patient plasma samples. Specific inhibitors of factors IXa and XIa were efficient in all 8 cases that we tested. Also, only factors IXa and XIa added to normal donors’ plasma induced SC formations from isolated centers, in a pattern similar to that in patients’ plasma. In contrast, factors VIIa, Va, tissue factor induced uniform plasma clotting. SC disappeared after high-speed centrifugation. However, phospholipid supplementation of centrifuged plasma returned them at least partially in 5 out of 22 patients’ plasmas, indicating some other role of microparticles than providing phospholipid surface. Circulating procoagulant microparticles isolated from plasma directly activated factor XII in buffer and in diluted plasma. Flow cytometry revealed an increase in procoagulant microparticles in patients’ plasmas with SC.Conclusion
Our data suggest that combination of circulating active factors (specifically, factors IXa and XIa) with circulating procoagulant and contact-pathway-activating microparticles is the predominant mechanism causing spontaneous clotting in patient plasma. 相似文献9.
Mary K. Yates Mithun R. Raje Payel Chatterjee Christina F. Spiropoulou Sina Bavari Mike Flint Veronica Soloveva Katherine L. Seley-Radtke 《Bioorganic & medicinal chemistry letters》2017,27(12):2800-2802
Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50 = 2 μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7 μM. 相似文献
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