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161.
Datta S Saha DR Ghosh D Majumdar T Bhattacharya S Mazumder S 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2007,145(3):339-349
We studied the hepatocellular alterations induced by sub-lethal concentrations (0.50 muM) of arsenic in Indian catfish Clarias batrachus L. Sub-lethal arsenic exposure altered serum aspartate aminotransferase and alkaline phosphatase levels and brought about significant changes in different serum biochemical parameters. Arsenic exposure reduced total hepatocyte protein content and suppressed the proliferation of hepatocytes in a time-dependent manner. Routine histological studies on liver documented arsenic-induced changes characterized by dilated sinusoids, formation of intracellular edema, megalocytosis, vacuolation and appearance of hepatic cells with distorted nuclei. Transmission electron microscopy of hepatocytes further revealed hyperplasia and hypertrophy of mitochondria, development of dilated rough endoplasmic reticulum and changes in peroxisome size with duration of arsenic exposure. Degeneration of mitochondrial cristae and condensation of chromatin was also evident in arsenic-exposed hepatocytes. A significant number of hepatocytes isolated from arsenic-exposed fish stained with annexin V and demonstrated DNA ladder characteristic of apoptosis. Single-cell gel electrophoresis of exposed hepatocytes also revealed the development of comets usually seen in apoptotic cells. Using specific inhibitors it was determined that the arsenic-induced apoptosis of hepatocytes was caspase-mediated, involving the caspase 3 pathway. 相似文献
162.
Bcl-2 family proteins and interleukin-1-beta converting enzyme/Caenorhabditis elegans cell death gene-3 (ICE/CED-3) family proteases (caspases) represent the basic regulators of apoptosis. However, the precise mechanism by which they interact is unclear. In this study, we found that gamma-radiation-induced apoptosis of leukemia cells was associated with activation of multiple caspases and bax up-regulation. Membrane changes and caspase activities were suppressed by specific caspase inhibitors. Similarly, the serine protease inhibitors z-Ala-Ala-Asp-cmk (AAD) and tosyl-lysine chloromethyl ketone (TLCK) also prevented caspase activation and poly(ADP-ribose) polymerase cleavage in vivo but had no effect on caspase activity in vitro. TLCK also prevented bax up-regulation as a result of its inhibitory effect on p53 function. Inhibitors of caspases and serine proteases partially prevented cell death, suggesting a caspase involvement in Bax-mediated cell death. We propose an ordering of signaling events in Bax-mediated cell death, including steps upstream and downstream of p53 and bax up-regulation. 相似文献
163.
Mondal SK Chakraborty G Gupta M Mazumder UK 《Indian journal of experimental biology》2006,44(1):39-44
Antioxidant activity of defatted methanol extract of D. malabarica bark was studied for its free radical scavenging property on different in vitro models e.g. 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitric oxide, superoxide, hydroxyl radical and lipid peroxide radical model. The extract showed good dose-dependent free radical scavenging property in all the models except in hydroxyl radical inhibition assay. IC50 values were found to be 9.16, 13.21, 25.27 and 17.33 microg/ml respectively in DPPH, nitric oxide, superoxide and lipid peroxidation inhibition assays. In hydroxyl radical inhibition assay 1000 microg/ml extract showed only 10% inhibition with respect to the control. Measurement of total phenolic compounds by Folin-Ciocalteu's phenol reagent indicated that 1 mg of the extract contained 120.7 microg equivalent of pyrocatechol. The results indicate that the antioxidant property of the extract may be due to the high content of phenolic compounds. However, the underlying mechanism may not involve hydroxyl radical scavenging property. 相似文献
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165.
Chen Q Chai YC Mazumder S Jiang C Macklis RM Chisolm GM Almasan A 《Cell death and differentiation》2003,10(3):323-334
Mitochondria play central roles in cellular metabolism and apoptosis and are a major source of reactive oxygen species (ROS). We investigated the role of ROS and mitochondria in radiation-induced apoptosis in multiple myeloma cells. Two distinct levels of ROS were generated following irradiation: a small increase observed early, and a pronounced late increase, associated with depletion of reduced glutathione (GSH) and collapse of mitochondrial membrane potential (deltapsi(m)). Exogenous ROS and caspase-3 induced deltapsi(m) drop and cytochrome c release from mitochondria, which could be prevented by molecular (dominant-negative caspase-9) and pharmacologic (zVAD-fmk) caspase inhibitors and overexpression of Bcl-2. Exogenous ROS also induced mitochondrial permeability transition (PT) pore opening and cytochrome c release in isolated mitochondria, which could be blocked by inhibition of PT with cyclosporin A. These results indicate that the late ROS production is associated with increased PT pore opening and decreased deltapsi(m), and GSH, events associated with caspase activation and cytochrome c release. 相似文献
166.
A novel sugar, 5,7-diacetamido-8-amino-3,5,7,8,9-pentadeoxy-d-glycero-d-galacto-non-2-ulosonic acid (NonlA), has been identified as a component of the oligosaccharide (OS) isolated from the lipooligosaccharide
(LOS) of the emerging strain of Vibrio parahaemolyticus O3:K6 associated with a global pandemic. In the present study we report the identification and characterization of this novel
sugar present in the OS of V. parahaemolyticus O3:K6, using chemical analysis, NMR spectroscopy and mass spectrometry. 相似文献
167.
The cysteine biosynthetic pathway is essential for survival of the protist pathogen Entamoeba histolytica, and functions by producing cysteine for countering oxidative attack during infection in human hosts. Serine acetyltransferase (SAT) and O-acetylserine sulfhydrylase (OASS) are involved in cysteine biosynthesis and are present in three isoforms each. While EhSAT1 and EhSAT2 are feedback inhibited by end product cysteine, EhSAT3 is nearly insensitive to such inhibition. The active site residues of EhSAT1 and of EhSAT3 are identical except for position 208, which is a histidine residue in EhSAT1 and a serine residue in EhSAT3. A combination of comparative modeling, multiple molecular dynamics simulations and free energy calculation studies showed a difference in binding energies of native EhSAT3 and of a S208H-EhSAT3 mutant for cysteine. Mutants have also been generated in vitro, replacing serine with histidine at position 208 in EhSAT3 and replacing histidine 208 with serine in EhSAT1. These mutants showed decreased affinity for substrate serine, as indicated by Km, compared to the native enzymes. Inhibition kinetics in the presence of physiological concentrations of serine show that IC50 of EhSAT1 increases by about 18 folds from 9.59 µM for native to 169.88 µM for H208S-EhSAT1 mutant. Similar measurements with EhSAT3 confirm it to be insensitive to cysteine inhibition while its mutant (S208H-EhSAT3) shows a gain of cysteine inhibition by 36% and the IC50 of 3.5 mM. Histidine 208 appears to be one of the important residues that distinguish the serine substrate from the cysteine inhibitor. 相似文献
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170.
Debika Datta Preeti Khatri Chaitali Banerjee Ambika Singh Ramavatar Meena Dhira Rani Saha Rajagopal Raman Paulraj Rajamani Abhijit Mitra Shibnath Mazumder 《PloS one》2016,11(1)
Mycobacterium fortuitum causes ‘mycobacteriosis’ in wide range of hosts although the mechanisms remain largely unknown. Here we demonstrate the role of calcium (Ca+2)-signalling cascade on M. fortuitum-induced apoptosis in headkidney macrophages (HKM) of Clarias sp. M. fortuitum could trigger intracellular-Ca+2 influx leading to the activation of calmodulin (CaM), protein kinase C alpha (PKCα) and Calmodulin kinase II gamma (CaMKIIg). Gene silencing and inhibitor studies established the role of CaM in M. fortuitum pathogenesis. We noted that CaMKIIg activation is regulated by CaM as well as PKCα-dependent superoxide anions. This is altogether first report of oxidised CaMKIIg in mycobacterial infections. Our studies with targeted-siRNA and pharmacological inhibitors implicate CaMKIIg to be pro-apoptotic and critical for the activation of extra-cellular signal regulated kinase 1/2 (ERK1/2). Inhibiting the ERK1/2 pathway attenuated nitric oxide synthase 2 (NOS2)-induced nitric oxide (NO) production. Conversely, inhibiting the NOS2-NO axis by specific-siRNA and inhibitors down-regulated ERK1/2 activation suggesting the crosstalk between ERK1/2 and NO is essential for pathogenesis induced by the bacterium. Silencing the NOS2-NO axis enhanced intracellular bacterial survival and attenuated caspase-8 mediated activation of caspase-3 in the infected HKM. Our findings unveil hitherto unknown mechanism of M. fortuitum pathogenesis. We propose that M. fortuitum triggers intracellular Ca+2 elevations resulting in CaM activation and PKCα-mediated superoxide generation. The cascade converges in common pathway mediated by CaMKIIg resulting in the activation of ERK1/2-NOS2 axis. The crosstalk between ERK1/2 and NO shifts the balance in favour of caspase dependent apoptosis of M. fortuitum-infected HKM. 相似文献