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111.
Alex Graça Contato Vanessa Kaplum Débora Botura Scariot Francielle Pelegrin Garcia Hugo Falzirolli Fábio Vandresen Tânia Ueda-Nakamura Sueli de Oliveira Silva Cleuza Conceição da Silva Celso Vataru Nakamura 《化学与生物多样性》2023,20(7):e202300523
Leishmaniasis is a tropical zoonotic disease. It is found in 98 countries, with an estimated 1.3 million people being affected annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N-methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity, and pancreatitis. Considering these aspects, this work aimed to obtain a new series of limonene-acylthiosemicarbazides hybrids as an alternative for the treatment of leishmaniasis. For this, promastigotes, axenic amastigotes, and intracellular amastigotes of Leishmania amazonensis were used in the antiproliferative assay; J774-A1 macrophages for the cytotoxicity assay; and electron microscopy techniques were performed to analyze the morphology and ultrastructure of parasites. ATZ−S-04 compound showed the best result in both tests. Its IC50, in promastigotes, axenic amastigotes and intracellular amastigotes was 0.35±0.08 μM, 0.49±0.06 μM, and 15.90±2.88 μM, respectively. Cytotoxicity assay determined a CC50 of 16.10±1.76 μM for the same compound. By electron microscopy, it was observed that ATZ−S-04 affected mainly the Golgi complex, in addition to morphological changes in promastigote forms of L. amazonensis. 相似文献
112.
113.
VAMP-2 and cellubrevin are expressed in pancreatic beta-cells and are essential for Ca(2+)-but not for GTP gamma S-induced insulin secretion. 总被引:9,自引:2,他引:7
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R Regazzi C B Wollheim J Lang J M Theler O Rossetto C Montecucco K Sadoul U Weller M Palmer B Thorens 《The EMBO journal》1995,14(12):2723-2730
VAMP proteins are important components of the machinery controlling docking and/or fusion of secretory vesicles with their target membrane. We investigated the expression of VAMP proteins in pancreatic beta-cells and their implication in the exocytosis of insulin. cDNA cloning revealed that VAMP-2 and cellubrevin, but not VAMP-1, are expressed in rat pancreatic islets and that their sequence is identical to that isolated from rat brain. Pancreatic beta-cells contain secretory granules that store and secrete insulin as well as synaptic-like microvesicles carrying gamma-aminobutyric acid. After subcellular fractionation on continuous sucrose gradients, VAMP-2 and cellubrevin were found to be associated with both types of secretory vesicle. The association of VAMP-2 with insulin-containing granules was confirmed by confocal microscopy of primary cultures of rat pancreatic beta-cells. Pretreatment of streptolysin-O permeabilized insulin-secreting cells with tetanus and botulinum B neurotoxins selectively cleaved VAMP-2 and cellubrevin and abolished Ca(2+)-induced insulin release (IC50 approximately 15 nM). By contrast, the pretreatment with tetanus and botulinum B neurotoxins did not prevent GTP gamma S-stimulated insulin secretion. Taken together, our results show that pancreatic beta-cells express VAMP-2 and cellubrevin and that one or both of these proteins selectively control Ca(2+)-mediated insulin secretion. 相似文献
114.
Genetic and cytological studies were conducted with a new male-sterile, female-fertile soybean [Glycine max (L.) Merr.] mutant. This mutant was completely male sterile and was inherited as a single-recessive gene. No differences in
female or male gamete transmission of the recessive allele were observed between reciprocal cross-pollinations in the F1 or F2 generations. This mutant was not allelic to any previously identified soybean genic male-sterile mutants: ms1, ms2, ms3, ms4, ms5, or ms6. No linkage was detected between sterility and flower color (W1 locus), or between sterility and pubescence color (T1 locus). Light microscopic and cytological observations of microsporogenesis in fertile and sterile anthers were conducted.
The structure of microspore mother cells (MMC) in male-sterile plants was identical to the MMCs in male-fertile plants. Enzyme
extraction analyses showed that there was no callase activity in male-sterile anthers, and this suggests that sterility was
caused by retention of the callose walls, which normally are degraded around tetrads at the late tetrad stage. The tapetum
from male-sterile anthers also showed abnormalities at the tetrad stage and later stages, which were expressed by an unusual
formation of vacuoles, and by accumulation of densely staining material. At maturity, anthers from sterile plants were devoid
of pollen grains.
Received: 13 May 1996 / Revision accepted: 19 August 1996 相似文献
115.
Homology modeling methods have been used to construct models of two proteins—the histidine-containing phosphocarrier protein (HPr) from Mycoplasma capricolum and human eosinophil-derived neurotoxin (EDN). Comparison of the models with the subsequently determined X-ray crystal structures indicates that the core regions of both proteins are reasonably well reproduced, although the template structures are closer to the X-ray structures in these regions—possible enhancements are discussed. The conformations of most of the side chains in the core of HPr are well reproduced in the modeled structure. As expected, the conformations of surface side chains in this protein differ significantly from the X-ray structure. The loop regions of EDN were incorrectly modeled—reasons for this and possible enhancements are discussed. © 1995 Wiley-Liss, Inc. 相似文献
116.
Amino acid oxidation and alanine production in rat hemidiaphragm in vitro. Effects of dichloroacetate. 总被引:1,自引:1,他引:0
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Dichloroacetate (an activator of pyruvate dehydrogenase) stimulates 14CO2 production from [U-14C]glucose, but not from [U-14C]glutamate, [U-14C]aspartate, [U-14C]- and [1-14C]-valine and [U-14C]- and [1-14C]-leucine. It is concluded (1) that pyruvate dehydrogenase is not rate-limiting in the oxidation to CO2 of amino acids that are metabolized to tricarboxylic acid-cycle intermediates, and (2) that carbohydrate (and not amino acids) is the main carbon precursor in alanine formation in muscle. 相似文献
117.
Activity of various glycosidases in the intracellular enzyme fraction of Bacteroides ovatus B4-11 was investigated. During 120 h of incubation at 37 degrees C, ca. 30% of the crude hemicellulose was hydrolyzed by an intracellular enzyme fraction of strain B4-11. Xylose was the major sugar released from crude hemicellulose. Glycosidases (alpha-1,6-glucosidase, alpha-1,4-glucosidase, beta-1,4-glucosidase, and beta-1,4-xylosidase) were induced in B. ovatus B4-11 by crude hemicellulose and heteroxylan. When B. ovatus B4-11 was grown on either crude hemicellulose or heteroxylan, the predominant enzyme in the intracellular enzyme fraction was beta-1,4-xylosidase. 相似文献
118.
D Abraham W F Blakemore A Dell M E Herrtage J Jones J T Littlewood J Oates A C Palmer R Sidebotham B Winchester 《The Biochemical journal》1984,222(1):25-33
A marked deficiency of alpha-L-fucosidase and the accumulation of fucose-containing glycoasparagines were found in the brains of two English Springer spaniels suffering from a progressive nervous disorder. Both forms of alpha-L-fucosidase in normal brain, which are separable by ion-exchange chromatography, are absent from the affected animals. The storage products were characterized by t.l.c., gel filtration, g.l.c. and fast-atom-bombardment mass spectrometry. The postulated structures of the main components are: (formula; see text) The enzymic defect and nature of storage products justify designation of this disorder as canine fucosidosis. 相似文献
119.
Molecular genetic and phenotypic alteration of Escherichia coli in natural water microcosms containing toxic chemicals 总被引:2,自引:0,他引:2
Abstract Microcosms of sterile Chesapeake Bay water were used to study effects of sub-lethal concentrations (1 μl/l) of nitrobenzene, m -cresol, and dibutyl phthalate on Escherichia coli H10407. E. coli remained viable during the 19-day test period in estuarine water, both in the presence and absence of the chemicals, long after it became non-culturable. Analysis of membrane proteins revealed changes in the protein composition. Carbohydrate and amino acid utilization was affected by these changes. Plasmids in E. coli H10407 could not be detected following microcosm exposure. When the cells were transferred to rich medium without toxic chemicals, growth resumed and plasmid bands were again detectable. 相似文献
120.
Summary The frequency and distribution of chiasmata was investigated in two fertile carriers of reciprocal translocations, one with a 46,XY,t(9;10)(p22;q24) karyotype and one with a 46,X,-Y,+der(Y),t(Y;10)(q12;q24) karyotype. In both cases the chromosomes involved in the translocation showed an increase in chiasma frequency in comparison to karyotypically normal controls and in both cases this increase was localised, affecting only one interstitial segment of each translocation quadrivalent. In the t(9;10) case chiasmata appeared in substantial numbers in a novel location, the proximal two thirds of 9p, while in the t(Y;10) case chiasmata appeared in a conventional location, the medial region of 10q, but at an increased frequency. Furthermore there was evidence for inter-chromosomal effects in the t(9;10) case. 相似文献