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Despite the existence of a preventative vaccine, HBV represents a substantial threat to public health, suggesting the need for research to develop new treatments to combat the disease. The authors review the available in vitro and in vivo models, including recently developed transgenic and chimeric mouse models. 相似文献
53.
Wiederhold L Leppard JB Kedar P Karimi-Busheri F Rasouli-Nia A Weinfeld M Tomkinson AE Izumi T Prasad R Wilson SH Mitra S Hazra TK 《Molecular cell》2004,15(2):209-220
The paradigm for repair of oxidized base lesions in genomes via the base excision repair (BER) pathway is based on studies in Escherichia coli, in which AP endonuclease (APE) removes all 3' blocking groups (including 3' phosphate) generated by DNA glycosylase/AP lyases after base excision. The recently discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the previously characterized OGG1 and NTH1, generate DNA strand breaks with 3' phosphate termini. Here we show that in mammalian cells, removal of the 3' phosphate is dependent on polynucleotide kinase (PNK), and not APE. NEIL1 stably interacts with other BER proteins, DNA polymerase beta (pol beta) and DNA ligase IIIalpha. The complex of NEIL1, pol beta, and DNA ligase IIIalpha together with PNK suggests coordination of NEIL1-initiated repair. That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals. 相似文献
54.
Metmyoglobin (Mb) was glycated by glucose in a nonenzymatic in vitro reaction. Amount of iron release from the heme pocket of myoglobin was found to be directly related with the extent of glycation. After in vitro glycation, the unchanged Mb and glycated myoglobin (GMb) were separated by ion exchange (BioRex 70) chromatography, which eliminated free iron from the protein fractions. Separated fractions of Mb and GMb were converted to their oxy forms -MbO2 and GMbO2, respectively. H2O2-induced iron release was significantly higher from GMbO2 than that from MbO2. This free iron, acting as a Fenton reagent, might produce free radicals and degrade different cell constituents. To verify this possibility, degradation of different cell constituents catalyzed by these fractions in the presence of H2O2 was studied. GMbO2 degraded arachidonic acid, deoxyribose and plasmid DNA more efficiently than MbO2. Arachidonic acid peroxidation and deoxyribose degradation were significantly inhibited by desferrioxamine (DFO), mannitol and catalase. However, besides free iron-mediated free radical reactions, role of iron of higher oxidation states, formed during interaction of H2O2 with myoglobin might also be involved in oxidative degradation processes. Formation of carbonyl content, an index of oxidative stress, was higher by GMbO2. Compared to MbO2, GMbO2 was rapidly auto-oxidized and co-oxidized with nitroblue tetrazolium, indicating increased rate of Mb and superoxide radical formation in GMbO2. GMb exhibited more peroxidase activity than Mb, which was positively correlated with ferrylmyoglobin formation in the presence of H2O2. These findings correlate glycation-induced modification of myoglobin and a mechanism of increased formation of free radicals. Although myoglobin glycation is not significant within muscle cells, free myoglobin in circulation, if becomes glycated, may pose a serious threat by eliciting oxidative stress, particularly in diabetic patients. 相似文献
55.
Goswami S Chatterjee S Bhattacharyya SN Basu S Adhya S 《Nucleic acids research》2003,31(19):5552-5559
Import of nucleus-encoded tRNAs into the mitochondria of the kinetoplastid protozoon Leishmania involves recognition of specific import signals by the membrane-bound import machinery. Multiple signals on different tRNA domains may be present, and further, importable RNAs interact positively (Type I) or negatively (Type II) with one another at the inner membrane in vitro. By co-transfection assays, it is shown here that tRNATyr (Type I) transiently stimulates the rate of entry of tRNAIle (Type II) into Leishmania mitochondria in transfected cells, and conversely, is inhibited by tRNAIle. Truncation and mutagenesis experiments led to the co-localization of the effector and import activities of tRNATyr to the D domain, and those of tRNAIle to the variable region–T domain (V-T region), indicating that both activities originate from a single RNA–receptor interaction. A third tRNA, human tRNALys, is imported into Leishmania mitochondria in vitro as well as in vivo. This tRNA has Type I and Type II motifs in the D domain and the V-T region, respectively, and shows both Type I and Type II effector activities. Such dual-type tRNAs may interact simultaneously with the Type I and Type II binding sites of the inner membrane import machinery. 相似文献
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RelB forms transcriptionally inactive complexes with RelA/p65 总被引:6,自引:0,他引:6
Marienfeld R May MJ Berberich I Serfling E Ghosh S Neumann M 《The Journal of biological chemistry》2003,278(22):19852-19860
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Role of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis of bone marrow derived stem cells 总被引:3,自引:0,他引:3
Macrophage colony stimulating factor (M-CSF) and osteoclast differentiation factor (ODF) regulate osteoclastogenesis in vivo. Regulation of osteoclast development in vitro by these cytokines has been reported in the present study. Simultaneous addition of ODF and M-CSF during initiation of bone marrow culture inhibited osteoclastogenesis. However, delayed addition of ODF (three days after initiation of the culture) resulted in dramatic increase in phenotypically and functionally mature osteoclast cells. Delayed addition of ODF beyond day three decreased osteoclastogenesis. Further, removal of M-CSF as early as day three inhibited ODF-induced osteoclastogenesis. These studies provided evidence for the importance of co-ordinated regulation of osteoclastogenesis by M-CSF and ODF. 相似文献
60.