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991.
992.
993.
The long-term effect of d-amphetamine (AMPH) on the induction of oxidative stress was examined in vivo in the rat brain. In this study, 2,3-dihydroxybenzoic acid (2,3-DHBA) and malonaldehyde (MDA) were used as the index of the hydroxyl radical and lipid peroxidation, respectively. The levels of 2,3-DHBA, MDA and dopamine (DA) in striatal homogenates were examined 7 days following injection of a single large dose of AMPH (7.5 mg/kg, i.p.) in rats pretreated with desipramine (10 mg/kg, i.p.), an agent that inhibits the metabolism of AMPH. Our results showed that 2,3-DHBA and MDA levels were significantly increased by AMPH, whereas DA and its metabolites, DOPAC and HVA were depleted in the striatum. Pretreatment with the glutamate NMDA receptor subtype antagonist MK-801 (1 mg/kg, i.p.) attenuated the increases of 2,3-DHBA and MDA, and provided partial protection against the long-lasting loss of DA produced by AMPH. Overall, the results demonstrate that AMPH could induce sustained production of free radical and oxidative damage, and lead to DA terminal degeneration in the striatum of the rat. 相似文献
994.
The co-incubation of morin hydrate with either doxorubicin or mitomycin C could minimize the toxicity of these anti-tumor drugs on cardiovascular cells, such as red blood cells, human umbilical vein endothelial cells (ECV304) and primary mouse cardiomyocytes, whereas morin hydrate did not lower the cytotoxicity of the drugs on human hepatocellular carcinoma cells (HepG2). Morin hydrate may not exert its antioxidant effect by enhancing the antioxidant enzymatic activity because it did not cause any induction on the mRNA levels of manganese superoxide dismutase expression in ECV304 cells and HepG2 cells. 相似文献
995.
Mitochondrial Ca(2+)homeostasis in the regulation of apoptotic and necrotic cell deaths 总被引:5,自引:0,他引:5
Using distinct models of apoptosis and necrosis, we have investigated the effect of mitochondrial Ca(2+)(Ca(m)) homeostasis in the regulation of cell death in neuroblastoma cells as well as cardiac myocytes. The steady state level of Ca(m)was determined as the FCCP-releasable Ca(2+). Culturing cells with low concentration of extracellular Ca(2+)(Ca(o)) or with EGTA triggered an early reduction in both the Ca(m)store and the membrane potential (DeltaPsi(m)). This was followed by the detection of cytochrome c release, caspase activation, and apoptosis. Inhibitors of the mitochondrial permeability transition pore such as cyclosporin A and Bcl-2 blocked the release of Ca(m)and inhibited apoptosis. In contrast, mitochondrial Ca(2+)overload resulted in necrotic cell death. Culturing cells in the presence of excess Ca(o)led to increased Ca(m)load together with a decrease of DeltaPsi(m)that reached maximum at 1 h, with necrosis occurring at 2 h. While the decline of Ca(m)and DeltaPsi(m)was a coupled reaction for apoptosis, this relationship was uncoupled during necrosis. Clonazepam, a relatively specific inhibitor of the mitochondrial Na/Ca exchanger, was able to protect the cells from necrosis by reducing Ca(m)overload. Importantly, combination of clonazepam and cyclosporin showed a cooperative effect in further reducing the Ca(m)overload and abolished cell death. The data imply the participation of Ca(m)homeostasis in the regulation of apoptosis and necrosis. 相似文献
996.
Characterization of lipid DNA interactions. I. Destabilization of bound lipids and DNA dissociation. 总被引:2,自引:0,他引:2 下载免费PDF全文
We have recently described a method for preparing lipid-based DNA particles (LDPs) that form spontaneously when detergent-solubilized cationic lipids are mixed with DNA. LDPs have the potential to be developed as carriers for use in gene therapy. More importantly, the lipid-DNA interactions that give rise to particle formation can be studied to gain a better understanding of factors that govern lipid binding and lipid dissociation. In this study the stability of lipid-DNA interactions was evaluated by measurement of DNA protection (binding of the DNA intercalating dye TO-PRO-1 and sensitivity to DNase I) and membrane destabilization (lipid mixing reactions measured by fluorescence resonance energy transfer techniques) after the addition of anionic liposomes. Lipid-based DNA transfer systems were prepared with pInexCAT v.2.0, a 4.49-kb plasmid expression vector that contains the marker gene for chloramphenicol acetyltransferase (CAT). LDPs were prepared using N-N-dioleoyl-N,N-dimethylammonium chloride (DODAC) and either 1, 2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). For comparison, liposome/DNA aggregates (LDAs) were also prepared by using preformed DODAC/DOPE (1:1 mole ratio) and DODAC/DOPC (1:1 mole ratio) liposomes. The addition of anionic liposomes to the lipid-based DNA formulations initiated rapid membrane destabilization as measured by the resonance energy transfer lipid-mixing assay. It is suggested that lipid mixing is a reflection of processes (contact, dehydration, packing defects) that lead to formulation disassembly and DNA release. This destabilization reaction was associated with an increase in DNA sensitivity to DNase I, and anionic membrane-mediated destabilization was not dependent on the incorporation of DOPE. These results are interpreted in terms of factors that regulate the disassembly of lipid-based DNA formulations. 相似文献
997.
A neutron reflectivity study of polymer-modified phospholipid monolayers at the solid-solution interface: polyethylene glycol-lipids on silane-modified substrates. 下载免费PDF全文
T L Kuhl J Majewski J Y Wong S Steinberg D E Leckband J N Israelachvili G S Smith 《Biophysical journal》1998,75(5):2352-2362
The structure of polymer-decorated phospholipid monolayers at the solid-solution interface was investigated using neutron reflectometry. The monolayers were composed of distearoylphosphatidylethanolamine (DSPE) matrixed with varying amounts of DSPE-PEG (DSPE with polyethylene glycol covalently grafted to its headgroup). Mixed lipid monolayers were Langmuir-Blodgett deposited onto hydrophobic quartz or silicon substrates, previously hydrophobized by chemically grafting a robust monolayer of octadecyltrichlorosilane (OTS). We show that this method results in homogeneous and continuous phospholipid monolayers on the silanated substrates and determine that the grafted PEG chains extend away from the monolayers into the solvent phase as a function of their density, as expected from scaling theories. In addition, ligands were coupled to the end of the PEG chains and selective binding was demonstrated using fluorescence microscopy. Our results demonstrate that these constructs are ideal for further characterization and studies with well-defined monomolecular films. 相似文献
998.
999.
Glucocorticoid-Dependent Action of Neural Crest Factor AP-2: Stimulation of Phenylethanolamine N-Methyltransferase Gene Expression 总被引:3,自引:3,他引:0
1000.
A new method of poly--hydroxybutyrate (PHB) extraction from recombinant E. coli is proposed, using homogenization and centrifugation coupled with sodium hypochlorite treatment. The size of PHB granules and cell debris in homogenates was characterised as a function of the number of homogenization passes. Simulation was used to develop the PHB and cell debris fractionation system, enabling numerical examination of the effects of repeated homogenization and centrifuge-feedrate variation. The simulation provided a good prediction of experimental performance. Sodium hypochlorite treatment was necessary to optimise PHB fractionation. A PHB recovery of 80% at a purity of 96.5% was obtained with the final optimised process. Protein and DNA contained in the resultant product were negligible. The developed process holds promise for significantly reducing the recovery cost associated with PHB manufacture.This revised version was published online in October 2005 with corrections to the Cover Date. 相似文献