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

We show that six mapped recessive lethal point mutations of the Notch locus affect mitochondrial enzyme activities: NADH oxidase, NADH dehydrogenase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase. The mutant N264-40, which has the same morphological and embryological effects as the Notch8 deletion, demonstrates the same biochemical effects and dosage relations as Notch8. The other five mapped recessive lethals also affect four enzymic activities. They show specific patterns of activity that depend in several cases on the wild-type chromosome in the heterozygous females. That effect occurs with mutants located in the extreme right part of the Notch locus where some mutations, according to other authors, show temperature-sensitive expression.
Genetics 1981 Sep
PMID:The action of the notchlocus in Drosophila melanogaster. II. Biochemical effects of recessive lethals on mitochondrial enzymes. 680 3

The genes encoding the NADH dehydrogenase subunits of respiratory complex I have not been identified so far in the mitochondrial DNA (mtDNA) of yeasts. In the linear mtDNA of Candida parapsilosis, we found six new open reading frames whose sequences were unambiguously homologous to those of the genes known to code for NADH dehydrogenase subunit proteins of different organisms, i.e., ND1, ND2, ND3, ND4L, ND5, and ND6. The gene for ND4 also appears to be present, as judged from hybridization experiments with a Podospora gene probe. Specific transcripts from these open reading frames (ND genes) could be detected in the mitochondria. Hybridization experiments using C. parapsilosis genes as probes suggested that ND genes are present in the mtDNAs of a wide range of yeast species including Candida catenulata, Pichia guilliermondii, Clavispora lusitaniae, Debaryomyces hansenii, Hansenula polymorpha, and others.
J Bacteriol 1994 Sep
PMID:NADH dehydrogenase subunit genes in the mitochondrial DNA of yeasts. 752 69

The status of glutathione (GSH) and protein thiol homeostasis was examined in rat brain regions during reperfusion after moderate and severe cerebral ischemia. GSH levels were decreased in brain regions during reperfusion for 1 hr after moderate or severe ischemia for 0.5 hr. Maximal loss of GSH (50-66%) was observed in the striatum and hippocampus. The GSH lost from the brain regions was essentially recovered as protein-glutathione mixed disulfide (PrSSG) with concomitant loss of protein thiols (PrSH). The activities of enzymes such as Na+K+ ATPase, NADH dehydrogenase and glutathione reductase were also inhibited but were restored after incubation of the brain homogenate with dithiothreitol. The depletion of GSH was also accompanied by an increase in the levels of malondialdehyde and reactive oxygen species. The total GSH recovered as sum of GSH and PrSSG was significantly higher than the sham-operated controls in the hippocampus and striatum after 1 hr of reperfusion, after moderate ischemia for 0.5 hr, and at the end of 24 hr of reperfusion the GSH-protein thiol homeostasis was restored. In contrast after 1 hr of reperfusion after severe ischemia, the GSH recovered as sum of GSH and PrSSG was not significantly different from sham-operated controls and at the end of 24 hr, 7 of 9 animals died. The recuperation of the brain from oxidative stress during reperfusion after moderate ischemia was thus preceded by increased recovery of total GSH essentially in the form of PrSSG. Thus, rapid restoration of thiol homeostasis in the brain during reperfusion may help the brain recover from reperfusion injury.
J Pharmacol Exp Ther 1995 Sep
PMID:Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. 756 84

The rate of transfer of reducing equivalents from cytoplasm to mitochondria has been examined in Ehrlich ascites tumour cells incubated in the presence of lactate. The flux of reducing equivalents was determined from the rate of metabolism of reduced intermediates that are oxidized within the cytosol. The magnitude of the flux of reducing equivalents was dependent on both the concentration of added lactate and the presence of carbohydrate. The rate of flux was twice as great in the presence of glucose and four times as high when glucose and lactate were added together as when lactate was the only added substrate. Fructose was less effective than glucose in stimulating reducing equivalent flux. In the presence of glucose or fructose, there was a substantial accumulation of hexose phosphates, dihydroxyacetone phosphate and glycerol 3-phosphate. Rotenone, an inhibitor of NADH dehydrogenase, and amino-oxyacetate, which inhibits the malate/aspartate shuttle, were powerful suppressors of reducing equivalent flux from lactate as sole substrate, but were much less potent in the presence of carbohydrate. Antimycin substantially inhibited reducing equivalent flux from all combinations of added substrates, consistent with its ability to block oxidation of reducing equivalents transferred by both the malate/aspartate and glycerol 3-phosphate shuttles. The glycerol 3-phosphate shuttle represents around 80% of the maximum total observed activity but is active only while glycolytic intermediates are present to provide the necessary substrates of the shuttle. This Ehrlich ascites cell line has an essentially similar total reducing equivalent shuttle capacity to that of isolated hepatocytes.
Biochem J 1995 Sep 01
PMID:Substrate-dependent utilization of the glycerol 3-phosphate or malate/aspartate redox shuttles by Ehrlich ascites cells. 765 9

The flat revertant cell line R1, isolated from human activated Ha-ras oncogene transformed NIH/3T3 cells (EJ-NIH/3T3) by mutagen treatment, expresses a variant form of the actin-regulatory protein gelsolin, designated p92-5.7. To clone the gene encoding p92-5.7, gelsolin cDNAs were isolated from a cDNA library of R1 cells. In vitro transcription-translation and nucleotide sequence analyses of the cloned cDNAs identified a point mutation in codon 321 at the cause for the expression of p92-5.7. Considering gelsolin's function as an actin binding protein, the expression of alpha-actin, which is downregulated in many transformed fibroblasts, was analyzed. In EJ-NIH/3T3 cells no alpha-actin transcript was detected, whereas in R1 cells alpha-actin mRNA expression was restored to a level similar to NIH/3T3 cells. Immunofluorescence staining of the cells with an alpha-actin specific monoclonal antibody did not detect any alpha-actin containing microfilaments in EJ-NIH/3T3 cells, but revealed an ordered microfilament pattern in R1 and NIH/3T3 cells. In order to identify other genetic alterations that may also contribute to the revertant phenotype, genes with an elevated expression in R1 cells compared with the parental EJ-NIH/3T3 cells were isolated by using a differential hybridization approach. The identified sequences represented mitochondrial (cytochrome b, cytochrome c oxidase subunit II, NADH dehydrogenase subunits 1 and 4) and alpha 2 (type I) collagen genes. In summary, these results suggest that a complex alteration of the expression of cytoskeletal, mitochondrial and extracellular matrix components is closely associated with the flat reversion of R1 cells.
Hokkaido Igaku Zasshi 1993 Sep
PMID:[A study on alterations of gene expression in a flat revertant R1 from ras-oncogene transformed NIH/3T3 cells]. 769 63

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.
Int J Cancer 1994 Sep 15
PMID:Down-regulation of mitochondrial gene expression by the anti-tumor arotinoid mofarotene (Ro 40-8757). 792 84

A mitochondrial DNA study of seven hydatidiform moles and seven full term placentas as controls was carried out to determine the role played by mitochondrial DNA as the only maternal genome participating in the pathogenesis of these trophoblastic growths. Mitochondrial DNA was digested by restriction enzymes Eco R1 and Hind III, processed by electrophoresis and stained by ethidium bromide. Molar mitochondrial DNA showed two restriction bands at 9416 and 2322 kbs with Eco R1 and one band at 2322 kbs with Hind III, whereas the controls showed three bands of 9416, 4361 and 2322 kbs with Eco 1, and two bands at 4361 and 2322 kbs with Hind III. The results were interpreted as a DNA alteration consistent with a mutation at level of tARN genes, initiating the reading of gen ND2 of Complex I, NADH dehydrogenase and affecting Complex CO III that transcribe cytochrome c and oxidoreductase genes. The alterations are considered as mutations probably resulted from folic acid deficiency at threshold levels during nuclear and mitochondrial DNA synthesis in oogenesis and meiosis that renders anucleated ova (cytoplasts), fertilized, and further accelerated development of a zygote bearing an entire androgenic genome.
Ginecol Obstet Mex 1994 Sep
PMID:[Mitochondrial heredity in hydatidiform moles]. 795 51

NADH dehydrogenase (EC 1.6.99.3) mutations at nucleotide 5460 of mitochondrial DNA (codon 331 of the ND2 subunit gene) have been associated with Alzheimer's disease (BBRC 182, 238-246, 1992; BBRC 189, 1202-1206, 1992). We have sequenced codons 304-347 of this gene in 15 neuropathologically confirmed cases of Alzheimer's disease. In addition, restriction enzyme analysis was performed on the same cases and on 28 control brains. No mutations were detected in the Alzheimer brains but heteroplasmy for a G-->A transition at nucleotide 5460 of mtDNA was found in the frontal cortex of a single control. Thus, our findings do not confirm reports of a significant association between mutations at nucleotide 5460 of mitochondrial DNA and Alzheimer's disease.
Biochem Biophys Res Commun 1994 Sep 15
PMID:No association of mutations at nucleotide 5460 of mitochondrial NADH dehydrogenase with Alzheimer's disease. 809 52

We have evaluated the effects of treatment with riboflavin in five patients with a mitochondrial myopathy, associated with a complex I (NADH dehydrogenase) deficiency. Two patients suffered from a clinically pure myopathy and the other patients presented with encephalomyopathic features. Treatment with riboflavin resulted in a clear clinical improvement in the two patients with the myopathic form of complex I deficiency. However, only one of the patients with the encephalomyopathic form improved during therapy. In three of the four patients in whom complex I activity in muscle tissue has been determined again during therapy, complex I activity appeared to be normalized. The clinical effects of treatment in this group of patients do not correlate well with normalization of complex I activity.
J Neurol Sci 1993 Sep
PMID:Treatment of complex I deficiency with riboflavin. 822 67

We have previously characterized mutant strains of Escherichia coli that are able to take over stationary-phase cultures. Here we describe two insertion mutations that prevent such strains from expressing this phenotype. Both insertions were mapped to min 51, and sequence analysis revealed that both mutated genes encode proteins homologous to subunits of mitochondrial NADH dehydrogenase I. Crude extracts prepared from both mutant strains were able to oxidize NADH but lacked the enzymatic activity needed to oxidize deamino-NADH, a substrate specific for NADH dehydrogenase I. This is the first identification of genes encoding subunits of NADH dehydrogenase I in E. coli. The significance of the inability of these mutant strains to compete in stationary-phase cultures is discussed.
J Bacteriol 1993 Sep
PMID:Escherichia coli mutants lacking NADH dehydrogenase I have a competitive disadvantage in stationary phase. 836 49


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