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181.
182.
The purpose of this study was to test the hypothesis that overexpression of glutathione reductase in transgenic Drosophila melanogaster increases resistance to oxidative stress and retards the aging process. Transgenic flies were generated by microinjection and subsequent mobilization of a P element construct containing the genomic glutathione reductase gene of Drosophila, with 4 kb upstream and 1.5 kb downstream of the coding region. Transgenic animals stably overexpressed glutathione reductase by up to 100% throughout adult life and under continuous exposure to 100% oxygen or air. Under hyperoxic conditions, overexpressors had increased longevity, decreased accrual of protein carbonyls, and dramatically increased survival rates after recovery from a semi-lethal dose of 100% oxygen. Under normoxic conditions, overexpression of glutathione reductase had no effect on longevity, protein carbonyl content, reduced glutathione, or glutathione disulfide content, although the total consumption of oxygen was slightly decreased. Glutathione reductase activity does not appear to be a rate-limiting factor in anti-aging defenses under normoxic conditions, but it may become a limiting factor when the level of oxidative stress is elevated. 相似文献
183.
AAM Coelho-Castelo AP Trombone RS Rosada RR Santos Jr VLD Bonato A Sartori CL Silva 《Genetic vaccines and therapy》2006,4(1):1-10
In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system. 相似文献
184.
A loss of about half of the trochlear motor neurons occurs during the course of normal development. The present investigation was undertaken to examine the role of afferent input in regulating the number of surviving or dying trochlear motor neurons. A majority of the afferent input to the trochlear nucleus comes from the vestibular nuclei of the hindbrain via the medial longitudinal fasciculus. Portions of the hindbrain were lesioned in duck embryos on embryonic day 3, considerably prior to the time motor neurons send their axons out and cell death begins. The effectiveness of hindbrain lesion was verified by electron microscopical examination of synapses. There was a significant decrease in the number of synapses on trochlear motor neurons following hindbrain lesion. Cell counts made after the period of cell death indicated a significant decrease in the final number of surviving trochlear motor neurons. Cell counts made prior to the onset of cell death indicated that there was a drastic reduction in the initial number of trochlear motor neurons produced in hindbrain lesion embryos. In spite of a significant reduction in the initial number of neurons, the percentage loss of neurons was about the same as during normal development. Since trochlear motor neurons are generated prior to the formation of afferent synapses on them, it is unlikely that the reduction in the number of motor neurons initially produced is due to reduced afferent synaptic input. Since the percentage of cell loss in hindbrain lesion and normal embryos is about the same, it seems that the magnitude of cell death is genetically programmed.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
185.
The generalized progressive retinal atrophies (gPRAs) form a group of retinal degenerations of pedigree dogs and cats, which have a variety of genetic origins (mostly unknown). We have examined the opsin gene for polymorphisms in several breeds of pedigree dog suffering from distinct forms of gPRA, by methods including single-strand conformation polymorphism analysis, microsatellite analysis and direct sequencing. The breeds examined included the Tibetan terrier, the miniature schnauzer, the Irish setter, the miniature poodle, the Labrador retriever and the English cocker spaniel, as well as individuals from breeds in which PRA has not been described and of mixed breed. Individuals from each of the named breeds suffering from PRA were compared with clinically normal dogs. Two polymorphisms were found. One, segregating within the Tibetan terrier population, but not seen in other breeds, was a synonymous transition at nucleotide position 780 in exon 3. Inheritance of this polymorphism suggests that opsin is unlikely to contain mutations causative of gPRA in this breed. The other polymorphism occurred between all miniature schnauzers examined and dogs of other breeds. It consisted of a single base insertion in intron 2. No polymorphisms in the opsin sequence were detected in any other breed. DNA sequencing allowed rigorous exclusion of mutations in opsin as a cause of gPRA in miniature poodles, English cocker spaniels or Labrador retrievers. 相似文献
186.
Based on a series of experiments, using cultured postmitotic neonatal rat cardiac myocytes as a model system, we present a novel hypothesis of lipofuscin formation. This hypothesis proposes that lipofuscin is formed within secondary lysosomes due to an interplay of two processes, the production of partially reduced oxygen species by mitochondria and the autophagocytotic degradation within secondary lysosomes. Specifically, it is proposed that H2O2 generated by mitochondria and other organelles permeates into the lumen of secondary lysosomes, which contain iron derived from cellular structures undergoing intralysosomal degradation. The interaction between reactive ferrous iron and H2O2 results, via Fenton-type mechanisms, in the generation of hydroxyl free radicals (OH), inducing lipid peroxidation and eventually leading to intermolecular cross-linking and lipofuscin formation. Additionally, mitochondria undergoing intralysosomal decomposition might continue for a certain period to produce superoxide anion radicals (O2-) and thus also H2O2. This model of lipofuscinogenesis could satisfactorily explain the variations observed in the rates of lipofuscinogenesis among different postmitotic cell types in various species. Such variations might arise from a variety of factors including differences in the efficiency of the 'anti-oxidative shield', rate of H2O2 generation, amount of chain-breaking antioxidants, mode of intralysosomal iron chelation, rate of autophagocytosis as well as degree of efficiency of the intralysosomal hydrolytic enzymes. 相似文献
187.
Myeloproliferative disorders frequently show deletions or rearrangements of the long arm of chromosome 13. We report here the cloning of RNF6, a new gene that maps close to the chromosome 13 breakpoint in a case of myelofibrosis with a t(4;13)(q26;q12). RNF6 is predicted to encode a 685-amino-acid protein with a coiled-coil domain and a RING-H2 finger at the amino and carboxy terminis, respectively. In addition, we have identified a novel motif, Lys-X-X-Leu/Ile-X-X-Leu/Ile (KIL motif), that is located shortly upstream of a subset of RING-H2 proteins, including RNF6. Drosophila g1, rat Neurodap1, and mouse Praja1. FISH and physical mapping indicated that RNF6 is located at 13q12.2 close to marker D13S1121, and it is oriented from telomere to centromere. RNF6 is not disrupted by the t(4;13). 相似文献
188.
189.
Mitochondrial DNA variation and genetic structure in populations of Drosophila melanogaster 总被引:5,自引:0,他引:5
The understanding of the genetic structure of a species can be improved by
considering together data from different types of genetic markers. In the
past, a number of worldwide populations of Drosophila melanogaster have
been extensively studied for several such markers, including allozymes,
chromosomal inversions, and quantitative characters. Here we present
results from a study of restriction- fragment-length polymorphisms of
mitochondrial DNA (mtDNA) in 92 isofemale lines from many of the same
geographic populations of D. melanogaster. Eleven restriction enzymes were
used, of which four revealed restriction-site polymorphism. A total of 24
different haplotypes were observed, of which 18 were unique to single
populations. In many populations, the unique haplotypes have reached high
frequency without being observed in neighboring populations. A Wagner
parsimony tree reveals that mutationally close variants show geographical
clumping, suggesting local differentiation of mtDNA in populations. The
Old-World and the New-World populations are differentiated, with the
predominant Old-World haplotype being virtually absent from the New World.
These results contrast with those for the nuclear genes, in which many loci
show parallel clines in different continents, and suggest a common origin
of D. melanogaster populations in North America.
相似文献
190.