Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro culture of mammalian preimplantation embryos is associated with various developmental disorders such as retardation in development and cell damage. The molecular mechanisms underlying these processes are poorly understood. One of the possible reasons may be the unphysiologically high oxygen concentration used for culture. Four-day-old rabbit blastocysts were cultured with 5% O2 (physiologic oxygen concentration) or 20% O2 (usually used for in vitro culture) for 4 hr. Differences in gene expression were analysed by differential display reverse-transcriptase polymerase chain reaction (DD RT-PCR). Thirty-two differentially expressed RNA bands were found. Two of them revealed a high sequence homology to the equine NADH-ubiquinone oxidoreductase chain 2 (ND2), a subunit of complex I of the respiratory chain. mRNA expression of ND2 was increased in blastocysts cultured with the higher oxygen concentration. Increased expression of ND2 was confirmed by semiquantitative and semiquantitative competitive RT-PCR.
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PMID:Increased expression of NADH-ubiquinone oxidoreductase chain 2 (ND2) in preimplantation rabbit embryos cultured with 20% oxygen concentration. 950 90

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a dopaminergic neurotoxin which inhibits mitochondrial complex I. 3-Nitropropionic acid (3-NPA) inhibits mitochondrial complex II and produces specific striatal lesions. In order to produce a combined striatal neuronal and dopaminergic afferent lesion, we administered both toxins simultaneously to the mouse. The combination brought about a lesion in the striatum that was not simply additive of the two combined toxins. Intriguingly, a group of striatal neurons became immunoreactive to tyrosine hydroxylase after day 1. Some of them were clearly visible up to the dendritic details. Immuno-electron microscopy indicated that the tyrosine hydroxylase-positive striatal neurons contained densely immunoreactive polyribosomes. Reverse transcriptase-polymerase chain reaction analysis indicated the up-regulation of tyrosine hydroxylase mRNA in the treated striatum. These neurons were also immunoreactive to aromatic L-amino acid decarboxylase.We conclude that the combined administration of MPTP and 3-NPA caused a more profound damage to the nigro-striatal dopaminergic system, and thus some striatal neurons capable of up-regulating tyrosine hydroxylase were induced to produce dopamine, probably to compensate for the dopamine depletion.
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PMID:Neuronal ectopic expression of tyrosine hydroxylase in the mouse striatum by combined administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 3-nitropropionic acid. 1173 97

A bush-type plant was selected from tropical pumpkin 'cga' (Cucurbita moschata Duchesne) in order to study the vine development in C. moschata. In this study, a novel gene encoding NADH dehydrogenase was isolated from the vine line (cgaV) of C. moschata, that was not expressed in the near isogenic bush line (cgaBu). This gene, designated as CmV1 (C. moschata vine 1), was 545 bp in length and was composed of a 477 bp open reading frame, which had 99% nucleotide similarity to the chloroplast ndhJ gene for NADH dehydrogenase subunit J from Brassica oleracea. The deduced amino acid sequence of CmV1 had 99% similarity to NADH dehydrogenase subunit J from Arabidopsis and had 98% similarity to NADH dehydrogenase subunit from Barbarea verna. Analysis of the basic characteristics of the CmV1 protein revealed that it has one Respiratory chain NADH dehydrogenase 30 kD subunit signature, three N-myristoylation sites, one Casein kinase II phosphorylation site, and one Protein kinase C phosphorylation site. Reverse transcriptase-PCR analysis showed that CmV1 was expressed at a high level in the internodes and hypocotyls and was expressed stronger in elongating internodes than in fully expanded internodes. In conclusion, results obtained in the present study suggest that CmV1 gene might play important roles in vine elongation of tropical pumpkin.
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PMID:Molecular cloning and expression of a bush related CmV1 gene in tropical pumpkin. 1930 73

Human noroviruses (family Caliciviridae) are the leading cause of nonbacterial gastroenteritis worldwide. Despite the prevalence of these viruses within the community, the study of human norovirus has largely been hindered due to the inability to cultivate the viruses ex vivo and the lack of a small-animal model. In 2003, the discovery of a novel murine norovirus (MNV-1) and the identification of the tropism of MNV-1 for cells of a mononuclear origin led to the establishment of the first norovirus tissue culture system. Like other positive-sense RNA viruses, MNV-1 replication is associated with host membranes, which undergo significant rearrangement during infection. We characterize here the subcellular localization of the MNV-1 open reading frame 1 proteins and viral double-stranded RNA (dsRNA). Over the course of infection, dsRNA and the MNV-1 RNA-dependent RNA polymerase (NS7) were observed to proliferate from punctate foci located in the perinuclear region. All of the MNV-1 open reading frame 1 proteins were observed to colocalize with dsRNA during the course of infection. The MNV-1 replication complex was immunolocalized to virus-induced vesicle clusters formed in the cytoplasm of infected cells. Both dsRNA and MNV-1 NS7 were observed to localize to the limiting membrane of the individual clusters by cryo-immunoelectron microscopy. We show that the MNV-1 replication complex initially associates with membranes derived from the endoplasmic reticulum, trans-Golgi apparatus, and endosomes. In addition, we show that MNV-1 replication is insensitive to the fungal metabolite brefeldin A and consistently does not appear to recruit coatomer protein complex I (COPI) or COPII component proteins during replication. These data provide preliminary insights into key aspects of replication of MNV-1, which will potentially further our understanding of the pathogenesis of noroviruses and aid in the identification of potential targets for drug development.
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PMID:Mouse norovirus replication is associated with virus-induced vesicle clusters originating from membranes derived from the secretory pathway. 1958 41

Eukaryotic positive-strand RNA viruses replicate using the membrane-bound replicase complexes, which contain multiple viral and host components. Virus infection induces the remodeling of intracellular membranes. Virus-induced membrane structures are thought to increase the local concentration of the components that are required for replication and provide a scaffold for tethering the replicase complexes. However, the mechanisms underlying virus-induced membrane remodeling are poorly understood. RNA replication of red clover necrotic mosaic virus (RCNMV), a positive-strand RNA plant virus, is associated with the endoplasmic reticulum (ER) membranes, and ER morphology is perturbed in RCNMV-infected cells. Here, we identified ADP ribosylation factor 1 (Arf1) in the affinity-purified RCNMV RNA-dependent RNA polymerase fraction. Arf1 is a highly conserved, ubiquitous, small GTPase that is implicated in the formation of the coat protein complex I (COPI) vesicles on Golgi membranes. Using in vitro pulldown and bimolecular fluorescence complementation analyses, we showed that Arf1 interacted with the viral p27 replication protein within the virus-induced large punctate structures of the ER membrane. We found that inhibition of the nucleotide exchange activity of Arf1 using the inhibitor brefeldin A (BFA) disrupted the assembly of the viral replicase complex and p27-mediated ER remodeling. We also showed that BFA treatment and the expression of dominant negative Arf1 mutants compromised RCNMV RNA replication in protoplasts. Interestingly, the expression of a dominant negative mutant of Sar1, a key regulator of the biogenesis of COPII vesicles at ER exit sites, also compromised RCNMV RNA replication. These results suggest that the replication of RCNMV depends on the host membrane traffic machinery.
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PMID:ADP ribosylation factor 1 plays an essential role in the replication of a plant RNA virus. 2309 52