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41.
In the present investigation, we have used adenosine triphosphatase (ATPase) activity as biochemical test of toxic action of lindane that was explained by lipid peroxidation model. Study was also undertaken to ascertain the potential protective role of alpha-lipoic acid (ALA) and vitamin E on the same parameters. Highly acute dose of lindane, i.e., 40 mg/kg bw for 18 h exposure, was used for creating lesions in brain. Lipid peroxidation was measured in terms of glutathione peroxidase and thio barbituric acid-reacting substances (TBARS). Various brain regions under investigation were cerebellum and pons-medulla oblongata. Healthy, male, Swiss mice (7–8 weeks old) were allocated into four groups. First group was control, second group was treated with lindane, third group was treated purely with antioxidants, and fourth group received both antioxidants and lindane treatment. Results revealed the significant difference (at 1% and 5% in all groups) in all studied parameters from control. Increased TBARS level in second group suggests that lindane enhances the production of free radicals in studied brain regions. Antioxidants under test are efficient remedy for neurotoxicity caused by lindane. We conclude that lindane manifests toxic effects on brain ATPase and enhances lipid peroxidation. ALA and vitamin E in combination may provide protection against lindane-induced acute toxicity. 相似文献
42.
The study is aimed at exploring the utility of thermoanalytical methods in the solid-state characterization of various crystalline
forms of nevirapine. The different forms obtained by recrystallization of nevirapine from various solvents were identified
using differential scanning calorimetry and thermogravimetric analysis (TGA). The appearance of desolvation peak accompanied
by weight loss in TGA indicated the formation of solvates: hemi-ethanolate (Form I), hemi-acetonitrilate (Form II), hemi-chloroformate
(Form III), hemi-THF solvate (Form IV), mixed hemi-ethanolate hemi-hydrate (Form V), and hemi-toluenate (Form VI). The higher
desolvation temperatures of all the solvates except toluenate than their respective boiling point indicate tighter binding
of solvent. Emphasis has been laid on the determination of heat capacity and heat of solution utilizing microreaction calorimeter
to further distinguish the various forms. The enthalpy of solution (ΔH
sol), an indirect measure of the lattice energy of a solid, was well correlated with the crystallinity of all the solid forms
obtained. The magnitude of ΔH
sol was found to be −14.14 kJ/mol for Form I and −2.83 kJ/mol for Form V in phosphate buffer of pH 2, exhibiting maximum ease
of molecular release from the lattice in Form I. The heat capacity for solvation (ΔC
p) was found to be positive, providing information about the state of solvent molecules in the host lattice. The solubility
and dissolution rate of the forms were also found to be in agreement with their enthalpy of solution. Form (I), being the
most exothermic, was found to be the most soluble of all the forms. 相似文献
43.
Several noncoding RNAs do vital cellular functions, including gene regulation and cell differentiation. Previously, we reported that vault RNA (vRNA) has the ability to recognize chemotherapeutic compounds, such as mitoxantrone, based on biophysical and biochemical analyses. In the present study, we show that human glioblastoma-, leukemia-, and osteocarcinoma-derived cell lines overexpress vRNA and exhibit higher resistance toward mitoxantrone. Interestingly, when vRNA expression was suppressed by RNA interference in these cells, the resistance progressively decreased. In agreement with these findings, overexpression of vRNA-1 caused resistance to mitoxantrone. These results suggest a role of vRNA in mitoxantrone resistance in malignant cells and justify further studies on the importance and application of noncoding RNAs in cancer chemotherapeutics. 相似文献
44.
Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes 总被引:8,自引:0,他引:8
Pospisilik JA Knauf C Joza N Benit P Orthofer M Cani PD Ebersberger I Nakashima T Sarao R Neely G Esterbauer H Kozlov A Kahn CR Kroemer G Rustin P Burcelin R Penninger JM 《Cell》2007,131(3):476-491
Type-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Recent studies place altered mitochondrial oxidative phosphorylation (OxPhos) as an underlying genetic element of insulin resistance. However, the causative or compensatory nature of these OxPhos changes has yet to be proven. Here, we show that muscle- and liver-specific AIF ablation in mice initiates a pattern of OxPhos deficiency closely mimicking that of human insulin resistance, and contrary to current expectations, results in increased glucose tolerance, reduced fat mass, and increased insulin sensitivity. These results are maintained upon high-fat feeding and in both genetic mosaic and ubiquitous OxPhos-deficient mutants. Importantly, the effects of AIF on glucose metabolism are acutely inducible and reversible. These findings establish that tissue-specific as well as global OxPhos defects in mice can counteract the development of insulin resistance, diabetes, and obesity. 相似文献
45.
Renu Bhardwaj Sukhbir Kaur Pramodh Kumar Nagar Hardesh Kumar Arora 《Plant Growth Regulation》2007,53(1):1-5
Brassinosteroids play an important role in growth and development of plants. They have been reported universally in all the
plants. The present study deals with the presence of these compounds in immature tea seeds. Five brassinosteroids, i.e. 6-deoxo-28-norcathasterone,
6-deoxo-28-norteasterone, 3-dehydro-6-deoxo-28-norteasterone, 6-deoxo-28-nortyphasterol and 6-deoxo-28-norcastasterone have
been isolated and identified by GC–MS. The identified brassinosteroids and their derivatives are active constituents of late
C-6 oxidation pathway, thereby suggesting the biosynthesis of brassinosteroids in tea seeds by late C-6 oxidation pathway. 相似文献
46.
In our search for synthetic substitutes for artemisinin and its derivatives we had earlier prepared a series of adamantane-based 1, 2, 4-trioxanes 5a-c which had shown promising activity against P. berghei in Swiss mice. We have further evaluated these and two new compounds (5d-e) against Plasmodium knowlesi W1, a virulent malaria parasite in rhesus monkeys, in the dose range of 40-80 mg/kg x 5 days by intramuscular route. Trioxanes 5b and 5c showed 100% protection and cure at 80 mg/kg x 5 days, while trioxane 5a showed 71% cure at this dose. Detailed studies again showed 50% curative effect of 5a at 40 mg/kg x 5 days treatment. 相似文献
47.
The rat glucocorticoid-induced receptor (rGIR) is an orphan G protein-coupled receptor awaiting pharmacological characterization. Among known receptors, rGIR exhibits highest sequence similarity to the neuropeptide Y (NPY)-Y(2) receptor (38-40%). The pharmacological profile of rGIR was investigated using (125)I-PYY(3-36), a Y(2)-preferring radioligand and several NPY analogs. rGIR displayed a similar displacement profile as reported for the Y(2) receptor, in that the Y(2)-selective C terminus fragments of NPY and PYY (NPY(3-36) and PYY(3-36)) showed high affinity binding and activation of rGIR (low nanomolar range). The rank order potency for displacement was NPY(3-36)>PYY(3-36)=NPY>NPY(13-36)>Ac, Leu NPY(24-36)>[D-Trp(32)]-NPY>Leu(31), Pro(34)-NPY=hPP. NPY and Y(2)-selective agonists NPY(3-36) and PYY(3-36) led to significant activation of (35)S-GTPgammaS binding to rGIR transfected cells. BIIE0246, a specific Y(2) antagonist, displaced (125)I-PYY(3-36) binding to rGIR with high affinity (95nM). Activation of (35)S-GTPgammaS binding by Y(2)-selective agonist in rGIR transfected cells was also completely abolished by BIIE0246. Our data report, for the first time, an interaction of NPY ligands with rGIR expressed in vitro, and indicate similarities between GIR and the NPY-Y(2) receptor. 相似文献
48.
Pandey GK Pandey A Reddy VS Deswal R Bhattacharya A Upadhyaya KC Sopory SK 《Journal of biosciences》2007,32(2):251-260
Entamoeba histolytica contains a novel calcium-binding protein like calmodulin, which was discovered earlier, and we have reported the presence
of its homologue(s) and a dependent protein kinase in plants. To understand the functions of these in plants, a cDNA encoding
a calcium-binding protein isolated from Entamoeba histolytica (EhCaBP) was cloned into vector pBI121 in antisense orientation and transgenic tobacco plants were raised. These plants showed
variation in several phenotypic characters, of which two distinct features, more greenness and leaf thickness, were inherited
in subsequent generations. The increase in the level of total chlorophyll in different plants ranged from 60% to 70%. There
was no major change in chloroplast structure and in the protein level of D1, D2, LHCP and RuBP carboxylase. These morphological
changes were not seen in antisense calmodulin transgenic tobacco plants, nor was the calmodulin level altered in EhCaBP antisense
plants.
The results of this paper have been granted US Patent No. 6,791,009. 相似文献
49.
We have previously shown that one of the potential mediators of the deleterious effects of high glucose on extracellular matrix protein (ECM) expression in renal mesangial cells is its metabolic flux through the hexosamine biosynthesis pathway (HBP). Here, we investigate further whether the hexosamines induce oxidative stress, cell-cycle arrest and ECM expression using SV-40-transformed rat mesangial (MES) cells and whether the anti-oxidant alpha-lipoic acid will reverse some of these effects. Culturing renal MES cells with high glucose (HG, 25 mM) or glucosamine (GlcN, 1.5 mM) for 48 h stimulates laminin gamma1 subunit expression significantly approximately 1.5 +/- 0.2- and 1.9 +/- 0.3-fold, respectively, when compared to low glucose (LG, 5 mM). Similarly, HG and GlcN increase the level of G0/G1 cell-cycle progression factor cyclin D1 significantly approximately 1.7 +/- 0.2- and 1.4 +/- 0.04-fold, respectively, versus LG (p < 0.01 for both). Azaserine, an inhibitor of glutamine:fruc-6-PO(4) amidotransferase (GFAT) in the HBP, blocks the HG-induced expression of laminin gamma1 and cyclin D1, but not GlcN's effect because it exerts its metabolic function distal to GFAT. HG and GlcN also elevate reactive oxygen species (ROS) generation, pro-apoptotic caspase-3 activity, and lead to mesangial cell death as revealed by TUNEL and Live/Dead assays. FACS analysis of cell-cycle progression shows that the cells are arrested at G1 phase; however, they undergo cell growth and hypertrophy as the RNA/DNA ratio is significantly (p < 0.05) increased in HG or GlcN-treated cells relative to LG. The anti-oxidant alpha-lipoic acid (150 microM) reverses ROS generation and mesangial cell death induced by HG and GlcN. Alpha-lipoic acid also reduces HG and GlcN-induced laminin gamma1 and cyclin D1 expression in MES cells. In addition, induction of diabetes in rats by streptozotocin (STZ) increases both laminin gamma1 and cyclin D1 expression in the renal cortex and treatment of the diabetic rats with alpha-lipoic acid (400 mg kg(-1) body weight) reduces the level of both proteins significantly (p < 0.05) when compared to untreated diabetic rats. These results support the hypothesis that the hexosamine pathway mediates mesangial cell oxidative stress, ECM expression and apoptosis. Anti-oxidant alpha-lipoic acid reverses the effects of high glucose, hexosamine and diabetes on oxidative stress and ECM expression in mesangial cells and rat kidney. 相似文献
50.
We have demonstrated that the expressions of small molecular weight G-protein, H-Ras, and its effector protein, Raf-1, are
increased in the retina in diabetes, and the specific inhibitors of Ras function inhibit glucose-induced apoptosis of retinal
capillary cells. This study is to examine the contributory roles for H-Ras in glucose-induced apoptosis of retinal endothelial
cells by genetic manipulation of functionally active H-Ras levels. Bovine retinal endothelial cells were transfected with
the plasmids of either wild type (WT), constitutively active (V12) or dominant-negative (N17) H-Ras. Glucose-induced increase
in apoptosis, nitric oxide (NO) levels and activation of NF-κB and caspase-3 were determined in these genetically manipulated
cells. Exposure of bovine retinal endothelial cells to 20 mM glucose significantly increased H-Ras activation as determined
by Raf-1 binding assay. Overexpression of V12 in the endothelial cells further increased their glucose-induced apoptosis by
40%, NO levels by about 50%, and activated NF-κB and caspase-3 by about 30–40% compared to the untransfected cells incubated
in 20 mM glucose. In contrast, overexpression of the inactive mutant, N17, inhibited glucose-mediated increases in apoptotic
cell death, NO levels and NF-κB and caspase-3 activation; the values were significantly different (p < 0.02) compared to those obtained from the untransfected cells incubated under similar conditions. Our findings demonstrate
that H-Ras activation is important in the activation of the specific signaling events leading to the accelerated retinal capillary
cell apoptosis in hyperglycemic conditions, suggesting the possible use of H-Ras inhibitors to inhibit the pathogenesis of
diabetic retinopathy. 相似文献