Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.5 (NADH dehydrogenase)
 2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the mechanism of action of the antitumor arotinoid mofarotene (Ro 40-8757), differential screening of cDNA libraries with cDNA probes prepared from treated or untreated breast-cancer cells was performed. Several genes were identified that appeared to be regulated by mofarotene, including a mitochondrial gene encoding a subunit of NADH dehydrogenase (NDI). This gene was down-regulated in the breast-cancer cell line MDA-MB-231 after treatment with the arotinoid for 3 to 6 hr. Down-regulation of NDI was detected in 2 other breast-carcinoma cell lines (ZR-75-I and MCF-7) and a pancreatic cancer cell line (BxPC3), but not in the normal fibroblast cell line Wi-38 or several other tumor cell lines. This effect was blocked by addition of cycloheximide to the medium. The retinoids, all-trans and 9-cis retinoic acids, did not affect the expression of NDI in MDA-MB-231 cells, demonstrating that mofarotene was not acting through the nuclear retinoic-acid receptors. In the estrogen-receptor-expressing breast-cancer line ZR-75-I, tamoxifen had no effect on NDI expression. The cytotoxic drugs doxorubicin, 5-FU and vincristine also had no effect on regulation of this gene. Two mitochondrial proteins encoded in the nucleus, ATPase beta subunit and mitochondrial transcription factor I, were not down-regulated by mofarotene. Addition of mofarotene to cells incubated in glucose-free medium led to their death. These results indicate that down-regulation of mitochondrial gene transcription is specific to mofarotene and may explain, in part, the anti-proliferative effects of this compound.
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PMID:Down-regulation of mitochondrial gene expression by the anti-tumor arotinoid mofarotene (Ro 40-8757). 792 84

In the present study, we investigated the effect of Ginkgo biloba extract, EGb 761, and one of its components, bilobalide, on gene expression of subunit 1 of mitochondrial NADH dehydrogenase (ND1) in PC12 cells. By Northern blot analysis we found a approximately 2-fold significant increase in NDI mRNA level, after 48 and 72 h exposure to 100 microg/ml EGb 761 and to 10 microg/ml bilobalide. We also evaluated, by oxygraphy measurements, mitochondrial respiration during state 3 and state 4. In cells treated with EGb 761 and bilobalide for 48 and 72 h, state 4 respiration was significantly decreased, and the respiratory control ratio was increased. These results provide evidence that EGb 761 and bilobalide exert their protective effects by up-regulating mitochondrial ND1 gene expression and by decreasing state 4 respiration, whose increase is thought to be responsible for oxidative damage.
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PMID:Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells. 1195 34

Sea urchins of the family Strongylocentrotidae have been important model systems in many fields of basic biology, yet knowledge of their evolutionary identities such as the phylogenetic relationships and divergence times remains limited. Here, I inferred molecular phylogenies of seven Strongylocentrotid species (Strongylocentrotus franciscanus, S. nudus, S. purpuratus, S. intermedius, S. droebachiensis, S. pallidus, and Hemicentrotus pulcherrimus) from the analyses of mitochondrial DNA sequences of 12SrDNA (349 nt), 12SrDNA-tRNA(gln) region (862 nt), and a combined sequence of cytochrome oxidase subunit I (COI, 1080 nt) and NADH dehydrogenase subunit I (NDI, 742 nt). The rate of sequence evolution and divergence times for each species were then estimated from the trees with reference to the time of separation between Strongylocentrotidae and Parechinidae, 35 to 50 MYA. The three trees agree well with each other, and the phylogeny is summarized by ((S. franciscanus, S. nudus), (H. pulcherrimus (S. purpuratus, S. intermedius (S. droebachiensis, S. pallidus)))). It is notable that the genus Strongylocentrotus consists of two distinct clades and that H. pulcherrimus branches off within Strongylocentrotus, implying assignment of a separate, monospecific genus to this species inappropriate. The rate of sequence evolution is calibrated to be 0.24%-0.34%/Myr in 12SrDNA, 0.25%-0.36%/Myr in 12SrDNA-tRNA(gln), and 0.65%-0.93%/Myr in COI-NDI combined sequences. S. purpuratus, in particular, shows the significantly higher rate of evolution in the 12SrDNA and 12SrDNA-tRNA(gln) regions compared to other species, suggesting careful use of its sequences in comparative studies. The two clades of Strongylocentrotidae seem to have split 13-19 MYA, and H. pulcherrimus branched off 7.2-14 MYA. In the former clade, S. franciscanus and S. nudus separated 5.7-8.1 MYA. In the latter clade, S. purpuratus, S. intermedius, and the clade of S. droebachiensis and S. pallidus diverged approximately 4.6-12 MYA, and the last two closest species separated 2.1-3.1 MYA.
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PMID:Molecular phylogenies and divergence times of sea urchin species of Strongylocentrotidae, Echinoida. 1277 24

The northern biotype of Echinococcus granulosus occurs in North America and northern Eurasia in life-cycles involving cervids. Previously, cervid isolates of E. granulosus from North America have been characterized using molecular genetic techniques as the G8 genotype. In this study, 5 isolates of E. granulosus were collected from 4 reindeer and 1 moose in north-eastern Finland. DNA sequences within regions of mitochondrial cytochrome c oxidase I (COI) and NADH dehydrogenase I (NI)I) genes and the internal transcribed spacer 1 (ITS-1) fragment of the ribosomal DNA were analysed. The mitochondrial nucleotide sequences were identical in all isolates, but high sequence variation was found in the ITS-1 region. Mitochondrial and nuclear sequences of the Finnish cervid E. granulosus and the camel strain (G6) of E. granulosus resembled closely each other. According to phylogenetic analyses, the Finnish isolates have close relationships also with the pig (G7) and cattle (G5) strains. Although some similarities were found with the previously published North American cervid strain (G8), particularly in the NDI sequence and some of the ITS-1 clones, the Finnish E. granulosus form represents a distinct, previously undescribed genotype of E. granulosus. The novel genotype is hereby named as the Fennoscandian cervid strain (G10).
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PMID:Molecular genetic characterization of the Fennoscandian cervid strain, a new genotypic group (G10) of Echinococcus granulosus. 1296 23