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31.
Shikha Bakshi Maninder Kaur Arpana Verma Sadhna Sharma 《Journal of biochemical and molecular toxicology》2023,37(8):e23386
Drug-induced liver injury (DILI) is an adverse outcome of the currently used tuberculosis treatment regimen, which results in patient noncompliance, poor treatment outcomes, and the emergence of drug-resistant tuberculosis. DILI is primarily caused by the toxicity of the drugs and their metabolites, which affect liver cells, biliary epithelial cells, and liver vasculature. However, the precise mechanism behind the cellular damage attributable to first-line antitubercular drugs (ATDs), as well as the effect of toxicity on the cell survival strategies, is yet to be elucidated. In the current study, HepG2 cells upon treatment with a high concentration of ATDs showed increased perforation within the cell, cuboidal shape, and membrane blebbing as compared with control/untreated cells. It was observed that ATD-induced toxicity in HepG2 cells leads to altered mitochondrial membrane permeability, which was depicted by the decreased fluorescence intensity of the MitoRed tracker dye at higher drug concentrations. In addition, high doses of ATDs caused cell damage through an increase in reactive oxygen species production in HepG2 cells and a simultaneous reduction in glutathione levels. Further, high dose of isoniazid (50–200 mM), pyrazinamide (50–200 mM), and rifampicin (20–100 µM) causes cell apoptosis and affects cell survival during toxic conditions by decreasing the expression of potent autophagy markers Atg5, Atg7, and LC3B. Thus, ATD-mediated toxicity contributes to the reduced ability of hepatocytes to tolerate cellular damage caused by altered mitochondrial membrane permeability, increased apoptosis, and decreased autophagy. These findings further emphasize the need to develop adjuvant therapies that can mitigate ATD-induced toxicity for the effective treatment of tuberculosis. 相似文献
32.
Juliette Gaëtan Sébastien Halary Maxime Millet Cécile Bernard Charlotte Duval Sahima Hamlaoui Amandine Hecquet Muriel Gugger Benjamin Marie Neha Mehta David Moreira Fériel Skouri-Panet Cynthia Travert Elodie Duprat Julie Leloup Karim Benzerara 《Environmental microbiology》2023,25(3):751-765
The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments. 相似文献
33.
David L. Musso Nariman B. Mehta Francis E. Soroko Robert M. Ferris Elizabeth B. Hollingsworth Bernard T. Kenney 《Chirality》1993,5(7):495-500
The synthesis of the enantiomers of bupropion, (rac)-2-tert-butylamino-3′-chloropropiophenone 1 (Wellbutrin®) is described. The enantiomers were compared with the racemate in both the tetrabenazine-induced sedation model and the inhibition of uptake of biogenic amine assay. No significant differences were found in their potencies to reverse tetrabenazine-induced sedation in mice or in their IC50 values as inhibitors of biogenic amine uptake into nerve endings obtained from mouse brain. © 1993 Wiley-Liss, Inc. 相似文献
34.
Application of abscisic acid (ABA) brings about stomatal closure within 30 min in epidermal peels of Vicia faba . A number of phenolic compounds antagonise the effect of ABA. Derivatives of benzoic acid, cinnamic acid, coumarin and flavonoids have been studied in order to establish structure – activity relationship. Derivatives of benzoic acid reverse the ABA effects. Coumarin, esculetin and three hydro derivatives of cinnamic acid fail to show the anti-ABA activity. Thus, the presence of parahydroxyl group and double bond in the side chain is necessary for anti-ABA activity. 相似文献
35.
Vibha Malhotra Sawhney I. M. Santha Michael P. Timko S. L. Mehta 《Journal of plant biochemistry and biotechnology.》1996,5(2):91-95
Lectin has been isolated and purified from Lathyrus sativus using ammonium sulphate precipitation followed by affinity chromatography. The molecular weight as determined by HPLC was found to be 42kD. The lectin is a tetramer, consisting of two types of subunits of which the heavier subunit consists of 2 polypeptides of mol wt of about 21 kD and 16 kD while the smaller subunits consists of two polypeptides of about 5kD as revealed by SDS-PAGE. The most potent sugar inhibitor of the Lathyrus lectin was found to be α-methyl D-mannoside. The N-terminal amino acid sequence was similar to that of pea lectin sequence. 相似文献
36.
37.
Padmaja Mehta Surekha Zingde Suresh Advani Hema Desai Balwant Gothoskar 《Molecular and cellular biochemistry》1995,144(2):153-165
Lectin-receptors on leukocyte and endothelial surfaces are becoming more important in the light of increasing evidence which implicates lectin-carbohydrate interactions in diverse physiological phenomena. This study reports the identification of a major 118 kDa granulocyte surface protein, (Protein 1a) which binds the lectin wheat germ agglutinin (WGA), and is distinctly different from reported WGA binding granulocyte membrane proteins. Protein 1a has been isolated from the Triton-soluble and Triton-insoluble lysates of normal individuals and patients with Chronic Myeloid Leukemia (CML) using a combination of differential solubilization, lectin affinity, ion exchange chromatography and HPLC. The protein from the detergent lysates of both normal and CML granulocytes has similar pI values, lectin affinities, and hydrophobicity. However, its solubility in Triton is different in the two cell types. In 71% of CML cases examined, Protein 1a exhibits decreased Triton solubility suggesting its increased association with the cytoskeleton (CSK). Stimulation of normal granulocytes with WGA leads to the translocation of the soluble form of Protein 1a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1a is sustained only under conditions of excess WGA and occupied receptor. The CSK disruptive agent dihydrocytochalasin B (H2CB) releases the insoluble form of the receptor into the Triton-soluble fraction. Investigation of a CSK-involving process such as ligand internalization revealed that CML granulocytes exhibit slower kinetics of internalization of fluorescent WGA molecules. Since Protein 1a is a major WGA receptor on the granulocyte surface, its decreased Triton solubility in CML granulocytes suggests that this may be one of the factors contributing to the defective receptor-mediated endocytosis of WGA by CML cells, arising as a consequence of altered membrane-CSK interaction — a nodal point in the signal transduction cascade. 相似文献
38.
Mittal Chandra K. Harrell William B. Mehta Chander S. 《Molecular and cellular biochemistry》1995,149(1):263-265
This study was designed to evaluate thein vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of3H-L-arginine to3H-L-citrulline. Different concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+), cadmium (Cd2+), lead (Pb2+) and calcium (Ca2+) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis. 相似文献
39.
Genetic Analysis of Myoblast Fusion: blown fuse Is Required for Progression Beyond the Prefusion Complex 总被引:11,自引:1,他引:10
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Stephen K. Doberstein Richard D. Fetter Anand Y. Mehta Corey S. Goodman 《The Journal of cell biology》1997,136(6):1249-1261
The events of myoblast fusion in Drosophila are dissected here by combining genetic analysis with light and electron microscopy. We describe a new and essential intermediate step in the process, the formation of a prefusion complex consisting of “paired vesicles.” These pairs of vesicles from different cells align with each other across apposed plasma membranes. This prefusion complex resolves into dense membrane plaques between apposed cells; these cells then establish cytoplasmic continuity by fusion of small areas of plasma membrane followed by vesiculation of apposed membranes. Different steps in this process are specifically blocked by mutations in four genes required for myoblast fusion. One of these genes, blown fuse, encodes a novel cytoplasmic protein expressed in unfused myoblasts that is essential for progression beyond the prefusion complex stage. 相似文献
40.
Coloboma Hyperactive Mutant Mice Exhibit Regional and Transmitter-Specific Deficits in Neurotransmission 总被引:3,自引:1,他引:2
Jacob Raber Prashant P. Mehta Max Kreifeldt Loren H. Parsons Friebert Weiss Floyd E. Bloom Michael C. Wilson 《Journal of neurochemistry》1997,68(1):176-186
Abstract: The mouse mutant coloboma ( Cm /+), which exhibits profound spontaneous hyperactivity and bears a deletion mutation on chromosome 2, including the gene encoding synaptosomal protein SNAP-25, has been proposed to model aspects of attention-deficit hyperactivity disorder. Increasing evidence suggests a crucial role for SNAP-25 in the release of both classical neurotransmitters and neuropeptides. In the present study, we compared the release of specific neurotransmitters in vitro from synaptosomes and slices of selected brain regions from Cm /+ mice with that of +/+ mice. The release of dopamine (DA) and serotonin (5-HT) from striatum, and of arginine vasopressin and corticotropin-releasing factor from hypothalamus and amygdala is calcium-dependent. Glutamate release from and content in cortical synaptosomes of Cm /+ mice are greatly reduced, which might contribute to the learning deficits in these mutants. In dorsal striatum of Cm /+ mutants, but not ventral striatum, KCI-induced release of DA is completely blocked and that of 5-HT is significantly attenuated, suggesting that striatal DA and 5-HT deficiencies may be involved in hyperactivity. Further, although acetylcholine failed to induce hypothalamic corticotropin-releasing factor release from Cm /+ slices, restraint stress increased plasma corticosterone levels in Cm /+ mice to a significantly higher level than in +/+ mice, suggesting an important role for arginine vasopressin in hypothalamic-pituitary-adrenal axis activation. These results suggest that reduced SNAP-25 expression may contribute to a region-specific and neurotransmitter-specific deficiency in neurotransmitter release. 相似文献