Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.5 (NADH dehydrogenase)
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Phylogenetic relationships within the Laudakia caucasia species group on the Iranian Plateau were investigated using 1708 aligned bases of mitochondrial DNA sequence from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNAGln, tRNAIle, tRNAMet, ND2, tRNATrp, tRNAAla, tRNAAsn, tRNACys, tRNATyr, and COI (subunit I of cytochrome c oxidase). The aligned sequences contain 207 phylogenetically informative characters. Three hypotheses for historical fragmentation of Laudakia populations on the Iranian Plateau were tested. In two hypotheses, fragmentation of populations is suggested to have proceeded along continuous mountain belts that surround the Iranian Plateau. In another hypothesis, fragmentation is suggested to have resulted from a north-south split caused by uplifting of the Zagros Mountains in the late Miocene or early Pliocene [5-10 MYBP (million years before present)]. The shortest tree suggest the later hypothesis, and statistical tests reject the other two hypothesis. The phylogenetic tree is exceptional in that every branch is well supported. Geologic history provides dates for most branches of the tree. A plot of DNA substitutions against dates from geologic history refines the date for the north-south split across the Iranian Plateau to 9 MYBP (late Miocene). The rate of evolution for this segment of mtDNA is 0.65% (0.61-0.70%) change per lineage per million years. A hypothesis of area relationships for the biota of the Iranian Plateau is generated from the phylogenetic tree.
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PMID:Phylogenetic relationships among Agamid lizards of the Laudakia caucasia species group: testing hypotheses of biogeographic fragmentation and an area cladogram for the Iranian Plateau. 975 22

Phylogenetic relationships among lizards of the families Anguidae, Anniellidae, Xenosauridae, and Shinisauridae are investigated using 2001 aligned bases of mitochondrial DNA sequence from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile), tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), and COI (subunit I of cytochrome c oxidase), plus the origin for light-strand replication (O(L)) between the tRNA(Asn) and the tRNA(Cys) genes. The aligned sequences contain 1013 phylogenetically informative characters. A well-resolved phylogenetic hypothesis is obtained. Because monophyly of the family Xenosauridae (Shinisaurus and Xenosaurus) is statistically rejected, we recommend placing Shinisaurus in a separate family, the Shinisauridae. The family Anniellidae and the anguid subfamilies Gerrhonotinae and Anguinae each form monophyletic groups receiving statistical support. The Diploglossinae*, which appears monophyletic, is retained as a metataxon (denoted with an asterisk) because its monophyly is statistically neither supported nor rejected. The family Anguidae appears monophyletic in analyses of the DNA sequence data, and statistical support for its monophyly is provided by reanalysis of previously published allozymic data. Anguid lizards appear to have had a northern origin in Laurasia. Taxa currently located on Gondwanan plates arrived there by dispersal from the north in two separate events, one from the West Indies to South America and another from a Laurasian plate to Morocco. Because basal anguine lineages are located in western Eurasia and Morocco, formation of the Atlantic Ocean (late Eocene) is implicated in the separation of the Anguinae from its North American sister taxon, the Gerrhonotinae. Subsequent dispersal of anguine lizards to East Asia and North America appears to have followed the Oligocene drying of the Turgai Sea. The alternative hypothesis, that anguine lizards originated in North America and dispersed to Asia via the Bering land bridge with subsequent colonization of Europe and Morocco, requires a phylogenetic tree seven steps longer than the most parsimonious hypothesis. North African, European, and West Asian anguines were isolated from others by the rapid uplift of Tibet in the late Oligocene to Miocene. Phylogenetic analysis of evolutionary changes in the gene encoding tRNA(Cys) suggests gradual reduction of dihydrouridine (D) stems by successive deletion of bases in some lineages. This evolutionary pattern contrasts with the one observed for parallel elimination of the D-stem in mitochondrial tRNAs of eight other reptile groups, in which replication slippage produces direct repeats. An unusual, enlarged TpsiC (T) stem is inferred for tRNA(Cys) in most species.
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PMID:Molecular phylogenetics, tRNA evolution, and historical biogeography in anguid lizards and related taxonomic families. 1041 21

A well-supported phylogenetic hypothesis is presented for gekkonid lizards of the genus Teratoscincus. Phylogenetic relationships of four of the five species are investigated using 1733 aligned bases of mitochondrial DNA sequence from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile), tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), and COI (subunit I of cytochrome c oxidase). A single most parsimonious tree depicts T. przewalskii and T. roborowskii as a monophyletic group, with T. scincus as their sister taxon and T. microlepis as the sister taxon to the clade containing the first three species. The aligned sequences contain 341 phylogenetically informative characters. Each node is supported by a bootstrap value of 100% and the shortest suboptimal tree requires 29 additional steps. Allozymic variation is presented for proteins encoded by 19 loci but these data are largely uninformative phylogenetically. Teratoscincus species occur on tectonic plates of Gondwanan origin that were compressed by the impinging Indian Subcontinent, resulting in massive montane uplifting along plate boundaries. Taxa occurring in China (Tarim Block) form a monophyletic group showing vicariant separation from taxa in former Soviet Central Asia and northern Afghanistan (Farah Block); alternative biogeographic hypotheses are statistically rejected. This vicariant event involved the rise of the Tien Shan-Pamir and is well dated to 10 million years before present. Using this date for separation of taxa occurring on opposite sides of the Tien Shan-Pamir, an evolutionary rate of 0.57% divergence per lineage per million years is calculated. This rate is similar to estimates derived from fish, bufonid frogs, and agamid lizards for the same region of the mitochondrial genome ( approximately 0.65% divergence per lineage per million years). Evolutionary divergence of the mitochondrial genome has a surprisingly stable rate across vertebrates.
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PMID:Vicariant patterns of fragmentation among gekkonid lizards of the genus Teratoscincus produced by the Indian collision: A molecular phylogenetic perspective and an area cladogram for Central Asia. 1041 26

Phylogenetic relationships among salamandrids of the "true" salamander clade are investigated using 2019 aligned base positions (713 parsimony informative) of 20 mitochondrial DNA sequences from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile), tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), and COI (subunit I of cytochrome c oxidase), plus the origin for light-strand replication (O(L)) between the tRNA(Asn) and the tRNA(Cys) genes. Parsimony analysis produces a robust phylogenetic estimate for the relationships of the major groups of "true" salamanders. Strong support is provided for the sister taxon relationship of Chioglossa and Mertensiella caucasica and for the placement of Salamandra and Mertensiella luschani as sister taxa. These relationships suggest two vicariant events between Europe and Anatolia caused by the formation of seaways in the Mediterranean Basin. Molecular divergence indicates an Early Miocene separation of Chioglossa and M. caucasica and a Late Miocene separation of Salamandra and M. luschani. The traditional phylogenetic hypothesis of a monophyletic Mertensiella is statistically rejected, indicating that southwestern and northeastern Anatolian populations have separate historical biogeographic origins. Therefore, we recommend placement of M. luschani in the genus Salamandra. Within M. luschani, six highly divergent lineages showing 7.6 to 10.1% pairwise sequence divergence are identified. Tests using four-taxon subsamples suggest that these lineages diverged nearly simultaneously in the Late Miocene, approximately 6 to 8 million years ago, when extensive uplifting of Anatolia occurred in response to the Arabian collision.
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PMID:Molecular phylogenetics and historical biogeography among salamandrids of the "true" salamander clade: rapid branching of numerous highly divergent lineages in Mertensiella luschani associated with the rise of Anatolia. 1127 35

Phylogenetic relationships among frogs of the genus Rana from western North America are investigated using 2013 aligned bases of mitochondrial DNA sequence from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile), tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), and COI (subunit I of cytochrome c oxidase), plus the origin for light-strand replication (O(L)) between the tRNA(Asn) and tRNA(Cys) genes. The aligned sequences contain 401 phylogenetically informative characters. A well-resolved phylogenetic hypothesis in which the Rana boylii species group (R. aurora, R. boylii, R. cascadae, R. muscosa, and R. pretiosa) is monophyletic is obtained. Molecular sequence divergence suggests that the R. boylii species group is approximately 8 million years old. The traditional hypothesis showing monophyly of the yellow-legged frogs (R. boylii and R. muscosa) is statistically rejected in favor of a hypothesis in which R. aurora, R. cascadae, and R. muscosa form a clade. Reanalyses of published nuclear ribosomal DNA restriction-site data and allozymic data support a monophyletic R. boylii group, but do not effectively resolve relationships among species within this group. Eight populations of R. muscosa form two major clades separated by a biogeographic break in the Sierra Nevada of California. This biogeographic break is broadly concordant with breaks found in four other amphibian and reptilian taxa. The two major clades within R. muscosa are estimated to have diverged approximately 2.2 million years before present. Each of these major clades contains two subgroups showing approximately 1.5 million years divergence, implicating climatic effects of Pleistocene glaciation in vicariance. The four distinct subgroups of R. muscosa separated by at least 1.4 million years of evolutionary divergence are suggested as potential units for conservation.
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PMID:Molecular phylogenetics of western North American frogs of the Rana boylii species group. 1128 98

Different species of bat can be morphologically very similar. In order to estimate the amount of cryptic diversity among European bats we screened the intra- and interspecific genetic variation in 26 European vespertilionid bat species. We sequenced the DNA of subunit 1 of the mitochondrial protein NADH dehydrogenase (ND1) from several individuals of a species, which were sampled in a variety of geographical regions. A phylogeny based on the mitochondrial (mt) DNA data is in good agreement with the current classification in the family. Highly divergent mitochondrial lineages were found in two taxa, which differed in at least 11% of their ND1 sequence. The two mtDNA lineages in Plecotus austriacus correlated with the two subspecies Plecotus austriacus austriacus and Plecotus austriacus kolombatovici. The two mtDNA lineages in Myotis mystacinus were partitioned among two morphotypes. The evidence for two new bat species within Europe is discussed. Convergent adaptive evolution might have contributed to the morphological similarity among distantly related species if they occupy similar ecological niches. Closely related species may differ in their ecology but not necessarily in their morphology. On the other hand, two morphologically clearly different species (Eptesicus serotinus and Eptesicus nilssonii) were found to be genetically very similar. Neither morphological nor mitochondrial DNA sequence analysis alone can be guaranteed to identify species.
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PMID:Cryptic diversity in European bats. 1152 2

The amounts of superoxide and hydrogen peroxide generated by mitochondria under physiological conditions can be enhanced by cellular stress. This study tested the hypothesis that the response to hemin-induced stress, which includes heme oxygenase-1 (HO-1) induction, predisposes to oxidative damage of mitochondrial DNA (mtDNA). Hepatic mitochondria from control, hemin-, and CO-exposed rats were incubated with tert-butyl hydroperoxide (tert-BH) or the NO donor 1,2,3,4-oxatriazolium, 5-amino-3- (3,4-dichlorophenyl)-chloride (GEA 3162). Mitochondrial total and oxidized glutathione (GSH and GSSG), total and free iron, and 8-oxo-7, 8-dihydro-2' deoxyguanosine (8-OHdG) were determined with and without oxidants. As expected, oxidation by tert-BH induced significant GSH depletion and increased amounts of free iron and 8-OhdG. Oxidant exposure rapidly produced a large mtDNA deletion involving the coding regions for cytochrome c oxidase (COX 1) and NADH dehydrogenase (ND1 and ND2). Hemin and CO greatly exacerbated susceptibility to the deletion of mtDNA by tert-BH, and this was attenuated by preincubation with GSH methyl ester. Analysis of mitochondria-associated proteins Bax and Bcl-xl in hemin- and CO-exposed rats showed significant responses, revealing interactions with apoptotic pathways. Thus, hemin-induced mitochondrial events sensitize a specific region of the mitochondrial genome to deletion, which is related to depletion of GSH and is not explained by effects of CO. This mtDNA damage is associated with altered expression of mitochondrial cell death proteins, thereby suggesting a novel mechanism for systemic or environmental pro-oxidants to influence apoptosis.
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PMID:Rapid mtDNA deletion by oxidants in rat liver mitochondria after hemin exposure. 1182 50

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

The mitochondrial rotenone-sensitive NADH:ubiquinone oxidoreductase (complex I) comprises more than 35 subunits, the majority of which are encoded by the nucleus. In Chlamydomonas reinhardtii, only five components (ND1, ND2, ND4, ND5 and ND6) are coded for by the mitochondrial genome. Here, we characterize two mitochondrial mutants (dum5 and dum17) showing strong reduction or inactivation of complex I activity: dum5 is a 1T deletion in the 3' UTR of nd5 whereas dum17 is a 1T deletion in the coding sequence of nd6. The impact of these mutations and of mutations affecting nd1, nd4 and nd4/nd5 genes on the assembly of complex I is investigated. After separation of the respiratory complexes by blue native (BN)-PAGE or sucrose gradient centrifugation, we demonstrate that the absence of intact ND1 or ND6 subunit prevents the assembly of the 850 kDa whole complex, whereas the loss of ND4 or ND4/ND5 leads to the formation of a subcomplex of 650 kDa present in reduced amount. The implications of our findings for the possible role of these ND subunits on the activity of complex I and for the structural organization of the membrane arm of the enzyme are discussed. In mitochondria from all the strains analyzed, we moreover detected a 160-210 kDa fragment comprising the hydrophilic 49 kDa and 76 kDa subunits of the complex I peripheral arm and showing NADH dehydrogenase activity.
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PMID:Impact of mutations affecting ND mitochondria-encoded subunits on the activity and assembly of complex I in Chlamydomonas. Implication for the structural organization of the enzyme. 1207 58

In vivo studies have indicated that systemically administered bilobalide, a sesquiterpene trilactone constituent of Ginkgo biloba leaf extracts, can reduce cerebral edema produced by triethyltin, decrease cortical infarct volume in certain stroke models, and reduce cerebral ischemia. In vitro and ex vivo studies indicate that bilobalide has multiple mechanisms of action that may be associated with neuroprotection, including its preservation of mitochondrial ATP synthesis, its inhibition of apoptotic damage induced by staurosporine or by serum-free medium, its suppression of hypoxia-induced membrane deterioration in the brain, and its actions of increasing the expression of the mitochondrial DNA-encoded COX III subunit of cytochrome c oxidase and the ND1 subunit of NADH dehydrogenase. As multiple modes of action may apply to bilobalide, it could be useful in developing therapy for disorders involving cerebral ischemia and neurodegeneration.
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PMID:Bilobalide and neuroprotection. 1245 32


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