Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64

The hydrolytic activity of the chicken liver F1-ATPase is strongly inhibited by detergents. The inhibition is concentration dependent and the highest value is obtained at the critical micelle concentration. Cationic and anionic detergents are good inhibitor of the enzyme, however the inhibition is correlated rather with the micelle size than the charge of the detergent as demonstrated by the inhibition observed with the non-ionic beta-D-alkyl glucosides. The effect of detergents upon subunits interactions was studied by trypsin limited proteolysis. Incubation with cholate results in the proteolytic cleavage of the alpha and gamma subunits whereas in the presence of DTAB also the beta subunit is digested. The small subunits delta and epsilon instead are not accessible when the enzyme is treated with both detergents. The results may suggest that hydrophobic areas of defined size located at the interface among alpha, beta and gamma subunit are crucial for the catalytic activity of the enzyme.
Biochem Mol Biol Int 1994 Jan
PMID:Effect of detergents on the chicken liver F1-ATPase: functional and structural aspects. 801 84

Plastids present in different tissues may vary morphologically and functionally, despite the fact that all plastids within the same plant contain identical genomes. This is achieved by regulation of expression of the plastid genome by tissue-specific factors, the mechanisms of which are not fully understood. The proton translocating ATP synthase/ATPase is a multisubunit complex composed of nine subunits, six encoded in the plastid and three in the nucleus. We have investigated the tissue-specific expression of the large ATP synthase gene cluster in spinach (Spinacia oleracea). This gene cluster encodes four of the six plastid-encoded ATP synthase genes. Transcript abundance, transcriptional activity, and transcript stability were investigated relative to gene dosage in root plastids and in stem, leaf, and flower chloroplasts. All three of these factors display significant tissue-specific variation. It was intriguing to discover that, although transcript abundance normalized to gene dosage varies in each tissue, transcript abundance as a proportion of the entire plastid RNA population in each tissue is not significantly different. Thus it appears that in these tissues the variation in transcription and stability of transcripts derived from the large ATP synthase gene cluster balances to yield an equivalent proportion of these transcripts in the plastid RNA population. Expression of this gene cluster in photosynthetic as well as non-photosynthetic tissues may facilitate the plasticity of structure and function which is characteristic of plastids.
Plant Mol Biol 1994 Jun
PMID:Tissue-specific expression of the large ATP synthase gene cluster in spinach plastids. 804 63

Five cDNAs for genes differentially expressed during fruit development of kiwifruit (Actinidia deliciosa var. deliciosa cv. Hayward) were isolated from a library made from young fruit, 8-10 days after anthesis. One gene (pKIWI503) has low levels of expression in young fruit but is induced late in fruit development and during fruit ripening, and has some homology to plant metallothionein-like proteins. The other four genes are highly expressed in young fruit with reduced expression in the later stages of fruit development. pKIWI504 has strong homology to plant metallothionein-like proteins and pKIWI505 exhibits homology to the beta-subunit of the mitochondrial ATP synthase gene. The two other genes (pKIWI501 and 502) encode proteins with no significant homology to other known sequences.
Plant Mol Biol 1994 Aug
PMID:Cloning and characterization of five cDNAs for genes differentially expressed during fruit development of kiwifruit (Actinidia deliciosa var. deliciosa). 807 3

The effect of aging on rat liver regeneration and on the FoF1-ATP synthase complex of isolated liver mitochondria was followed after partial (70%) hepatectomy. ATP hydrolase activity in submitochondrial particles prepared from regenerating liver was first depressed; the time needed to reach the lowest activity was age dependent. This decrease was accompanied by parallel decrease of i) the respiratory rate of succinate supplemented mitochondria in state III; ii) the respiratory control index; iii) the rate of synthesis of ATP in succinate supplemented submitochondrial particles. This first phase of liver regeneration, characterized at all ages by a lag phase in the growth, was followed by a second phase in which the tissue mass was restored and the enzyme activities normalized. Immunoblot analysis showed that the changes in the catalytic activities of the FoF1-ATP synthase observed during liver regeneration were accompanied by parallel changes in the amount of subunits of both the catalytic (F1) and the membrane (Fo) sector of the complex.
Biochem Mol Biol Int 1994 May
PMID:Age dependent changes in mitochondrial FoF1 ATP synthase in regenerating rat-liver. 808 Dec 1

The effects of ethanol (12.5-500 mM for up to 24 h) on mitochondrial structure including that of ATPase particles in cultured ventricular myocardial cells were studied using negative-stain electron microscopy. The activity of mitochondrial ATPase after ethanol treatment was also examined cytochemically and biochemically. At 5 min after the addition of all the concentrations of ethanol examined, some mitochondrial cristae were expanded and the arrangement of mitochondrial ATPase particles on these cristae was disordered. At and after 30 min the cristae decreased in number and some were expanded, vesiculated or fragmented. ATPase particles also decreased in number, particularly after the application of ethanol in concentrations of more than 50 mM. All the mitochondria had broadened and translucent cristae, and lacked ATPase particles with 200 and 500 mM ethanol at 24 h, although with 12.5 and 50 mM ethanol some mitochondria had similar negatively stained images but others had ATPase particles on broadened cristae. The enzymatic activity of the mitochondrial ATPase was unchanged with 200 and 500 mM ethanol at 24 h, compared with controls. The cytochemical technique also detected enzyme activity with all the concentrations of ethanol examined at 24 h. The discrepancy between the structural and biochemical alterations in mitochondrial ATPase induced by ethanol is discussed.
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Ethanol-elicited structural and biochemical alterations in mitochondrial ATPase in cultured myocardial cells. 810 Jun 60

It has been previously reported (R. W. Steigerwalt et al., Mol. Carcinog., 5:32-40, 1992) that primary cultures of rat tracheal epithelial (RTE) cells and immortalized RTE cell lines produce three mRNA transcripts [2.5, 1.9, 1.4 kilobases (kb)] which hybridize to a murine transforming growth factor beta 1 (TGF-beta 1) complementary DNA probe. In this report, we show that the 1.9- and 1.4-kb transcripts are not detectable by Northern analysis of resting adult trachea but are induced in regenerating tracheal grafts and tumors formed from transformed RTE cells. Northern analysis of the TGF-beta 1 transcripts with subclones of the murine complementary DNA demonstrate that the 1.4-kb transcript lacks much of the 5' untranslated region (UTR). RNase protection analysis was used to map the transcriptional start site of the 1.4-kb transcript to within 30-40 base pairs of the first ATG codon. No differences in the coding or 3' UTR were detected between the 1.4-kb and the 2.5-kb transcripts. Although RTE cells produce a 1.9-kb TGF-beta 1 mRNA, we were unable to detect a previously reported unique 3' UTR, which we found to be almost identical to a rat mitochondrial ATPase sequence. Because the 1.4-kb transcript is missing most of the long GC-rich 5' UTR, it may be translated at a different rate than the 2.5- and 1.9-kb transcripts, or it may code for an intracellular form of TGF-beta 1. The 1.4-kb transcript has been observed under several conditions of injury or stress and, therefore, may be an important component of the TGF-beta 1 response to these conditions.
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PMID:Characterization of a third transforming growth factor beta 1 transcript in rat tracheal epithelial cells. 811 25

The mitochondrial F1-ATPase beta subunit (ATPase-beta) of Nicotiana plumbaginifolia is nucleus-encoded as a precursor containing an NH2-terminal extension. By sequencing the mature N. tabacum ATPase-beta, we determined the length of the presequence, viz. 54 residues. To define the essential regions of this presequence, we produced a series of 3' deletions in the sequence coding for the 90 NH2-terminal residues of ATPase-beta. The truncated sequences were fused with the chloramphenicol acetyl transferase (cat) and beta-glucuronidase (gus) genes and introduced into tobacco plants. From the observed distribution of CAT and GUS activity in the plant cells, we conclude that the first 23 amino-acid residues of ATPase-beta remain capable of specifically targeting reporter proteins into mitochondria. Immunodetection in transgenic plants and in vitro import experiments with various CAT fusion proteins show that the precursors are processed at the expected cleavage site but also at a cryptic site located in the linker region between the presequence and the first methionine of native CAT.
Plant Mol Biol 1994 Feb
PMID:Truncated presequences of mitochondrial F1-ATPase beta subunit from Nicotiana plumbaginifolia transport CAT and GUS proteins into mitochondria of transgenic tobacco. 815 82

The NAM1 nuclear gene was shown to control the stability and/or processing of mitochondrial transcripts of the cytochrome b, cytochrome oxidase subunit I and ATP synthase subunit VI genes [Groudinsky O., Bousquet I., Wallis M. G., Slonimski, P. P. & Dujardin G. (1993) Mol. Gen. Genet. 240, 419-427]. In order to better understand the mode of action of the NAM1 gene product, we have examined its intracellular fate. A fusion plasmid enabling bacterial over-expression of the corresponding protein-A-NAM1 cognate was constructed and subsequently employed as an antigen to raise polyclonal antibodies. These antibodies specifically recognise a 50-kDa protein which purifies along with the mitochondria and corresponds to NAM1p. Submitochondrial localisation experiments show that NAM1p is a soluble protein, located interior to the mitoplasts. Matricial location is a strong argument in favour of a direct interaction of NAM1p with particular mitochondrial transcripts and leads us to propose a model in which NAM1p could be an RNA-convoying protein stabilising and directing mitochondrial transcripts towards the inner face of the inner membrane where translation and assembly seem to occur.
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PMID:The NAM1 protein (NAM1p), which is selectively required for cox1, cytb and atp6 transcript processing/stabilisation, is located in the yeast mitochondrial matrix. 820 Mar 49

Exposure of purified mitochondrial F0F1 ATP synthase to H2O2 resulted in a marked inhibition of the ATPase activity, irrespective of the purification procedure used and of the incorporation of the enzyme complex into phospholipid vesicles. The inactivation appeared consequent to oxidative modifications of the F1 moiety, whereas damage to the F0 sector, leading to low enzyme activity through impaired binding with F1, seemed not to occur. In fact, when H2O2-inactivated complex was deprived of F1, no loss of the capacity of the F0 sector thus obtained to properly reassemble with untreated purified F1 was apparent, because the resulting enzyme complex showed full activity and oligomycin sensitivity. On the contrary, the exposure of the isolated components F1 or F0 to H2O2, followed by reassembly with untreated F0 and F1 respectively, resulted in both cases in lower catalytic activity of the reconstituted complexes, whereas low oligomycin sensitivity was exhibited only in the case of F0 treatment, suggesting the inactivation in this case as due to oxidative modifications leading to impaired binding with F1.
Biochem Mol Biol Int 1993 Aug
PMID:H2O2-induced damage to beef heart mitochondria F0F1 ATP synthase complex: differential sensitivity of the F1 and F0 moieties. 822 Feb 52


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