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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the rabbit model, we showed that partial outlet obstruction of the urinary bladder causes significant changes in the status and expression of the mitochondrial (mt) genetic system in bladder smooth muscle immediately after obstruction is initiated. Here we investigate quantitatively the severity of the mt genetic response to partial outlet obstruction in both short- and long-term obstructed rabbits. Based on previous functional studies, bladders with mass < 6 fold greater than control were considered compensated; bladders with mass > 6 fold that of control were considered decompensated. Analyses of DNA from compensated rabbit bladders showed that relative mt genome copy number decreased to 30% of control values. Transcript analyses for these samples showed that mt RNA levels increased 3 fold to compensate for lower template copy number. Analysis of decompensated bladders demonstrated that mt genome copy number increased to approximately 90% of control levels; mt transcripts progressively decreased in these samples by as much as 30 fold. In contrast, transcription of a mt-related nuclear gene decreased 3-9 fold in compensated bladders but increased 10-30 fold in decompensated bladders. Activity for the cytochrome oxidase complex, and for the mt enzyme citrate synthase, decreased steadily with increasing bladder hypertrophy. These data suggest that bladder dysfunction following partial outlet obstruction is mediated partly by a significant loss in mt and mt-related nuclear gene coordination.
Mol Cell Biochem 1997 Aug
PMID:Transcription of mitochondrial and mitochondria-related nuclear genes in rabbit bladder following partial outlet obstruction. 927 59

There is increasing evidence that a defect of the mitochondrial respiratory chain is implicated in the development of Parkinson disease. Decreased complex I activity of the mitochondrial respiratory chain has been reported in platelets, muscle, and brain of patients with Parkinson disease. Extrapyramidal symptoms (e.g. parkinsonism and dystonic reactions) are major limiting side effects of neuroleptics. Experimental evidence suggests that neuroleptics inhibit complex I in rat brain. There has not been a study of the effects of neuroleptics in human tissue, however. We therefore analyzed the activities of complexes I + III, complexes II + III, succinate dehydrogenase, complex IV (cytochrome c oxidase), and of citrate synthase in normal human brain cortex after the addition of haloperidol and chlorpromazine and the atypical neuroleptics risperidone, zotepine, and clozapine. Activity of complex I was progressively inhibited by all neuroleptics. Half-maximal inhibition (IC50) was 0.1 mM for haloperidol, 0.4 mM for chlorpromazine, and 0.5 mM for risperidone and zotepine. Clozapine had no effect on enzyme activity at concentrations up to 0.5 mM, followed by a slow decline with a maximum inhibition of 70% at 10 mM. IC50 was at about 2.5 mM. Thus, the concentration of clozapine needed to cause 50% inhibition of the activity of complexes I and III was about 5 times that of zotepine and risperidone, about 6 times that of chlorpromazine, and 25 times that of haloperidol. The inhibition thus paralleled the incidence of extrapyramidal effects caused by the different neuroleptics as they are known from numerous clinical studies. Our data support the hypothesis that neuroleptic-induced extrapyramidal side effects may be due to inhibition of the mitochondrial respiratory chain.
Mol Cell Biochem 1997 Sep
PMID:Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics. 930 97

The coding region of the mitochondrial citrate synthase gene (CIT1) from Saccharomyces cerevisiae was amplified by PCR and cloned into an expression vector (pAL4) downstream of the alcohol dehydrogenase (alcA) promoter of Aspergillus nidulans to yield pALCS1. Transformation of A. nidulans A773 with this construct gave stable transformants, AYC#1 and AYC#2, that were phenotypically stable for several mitotic divisions. Southern blot analysis showed that the CIT1 gene was successfully integrated into the chromosomes of the transformants. Western blot analysis and enzymatic assay for citrate synthase revealed that the integrated yeast gene was subject to inducible expression controlled by alcA promoter, which can be induced by threonine.
Mol Cells 1997 Aug 31
PMID:Inducible expression of yeast mitochondrial citrate synthase in Aspergillus nidulans. 933 92

Lipocortin 1 (LC1) is a 37 kDa member of the annexin family of proteins. It has been proposed to act as a mediator of some of the actions of glucocorticoids in anti-inflammatory and immune suppressive functions. LC1 has been shown to play a role in cell proliferation, apoptosis, and differentiation. However, the exact biological functions of LC1 still remain obscure. Here it is shown that LC1 displays a chaperone-like function. Stoichiometric amounts of LC1 suppressed thermally induced inactivation and aggregation of the test enzymes citrate synthase and glutamate dehydrogenase. LC1 was also effective in refolding guanine hydrochloride-denatured glutamate dehydrogenase, as judged by circular dichroism spectroscopy.
Biochem Mol Biol Int 1997 Oct
PMID:Chaperone-like function of lipocortin 1. 935 70

Citrate synthase which condenses acetyl-CoA and oxaloacetate to citrate was purified from Drosophila melanogaster. Some physicochemical as well as enzymatical properties were investigated. The optimum pH and temperature were pH 8.0-9.0 and 45 degrees C, respectively. The molecular weight of the enzyme was determined as 81,000 Da by gel filtration and the purified active enzyme consisted of two identical subunits which had a molecular mass of 48,700 on SDS-PAGE. Homogeneity of the purified enzyme was confirmed by SDS-PAGE and also by N-terminal amino acid sequence analysis. The Michaelis constants (K(m)) of the enzyme for acetyl-CoA and oxaloacetate were 6.7 microM and 3.1 microM, respectively. Kinetic studies showed that citrate synthase follows the concerted mechanism which forms a ternary complex. Propionyl-CoA, ATP, and intermediates of the TCA cycle, succinyl-CoA and alpha-ketoglutarate, behaved as inhibitors in vitro. Using pig and chicken heart enzymes for comparison, we found similarities at the N-terminal region. However, in the Ouchterlony immunodiffusion test, the polyclonal antibody raised against Drosophila citrate synthase did not show any crossreaction with pig, chicken or pigeon enzymes.
Mol Cells 1997 Oct 31
PMID:Characterization of citrate synthase purified from Drosophila melanogaster. 938 45

Little information is presently available concerning mitochondrial respiratory and oxidative phosphorylation function in the normal human heart during growth and development. We investigated the levels of specific mitochondrial enzyme activities and content during cardiac growth and development from the early neonatal period (10-20 days) to adulthood (67 years). Biochemical analysis of enzyme specific activities and content and mitochondrial DNA (mtDNA) copy number was performed with left ventricular tissues derived from 30 control individuals. The levels of cytochrome c oxidase (COX) and complex V specific activity, mtDNA copy number and COX subunit II content remained unchanged in contrast to increased citrate synthase (CS) activity and content. The developmental increase in CS activity paralleled increasing CS polypeptide content, but was neither related to overall increases in mitochondrial number nor coordinately regulated with mitochondrial respiratory enzyme activities. Our findings of unchanged levels of cardiac mitochondrial respiratory enzyme activity during the progression from early childhood to older adult contrasts with the age-specific regulation found with CS, a Krebs cycle mitochondrial enzyme.
Mol Cell Biochem 1998 Feb
PMID:Human mitochondrial function during cardiac growth and development. 954 45

Twelve pairs of healthy sedentary males matched for their body mass index (BMI) with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR; controls) to a standardized glucose infusion test (GIT) were studied in respect to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI), and peripheral insulin sensitivity (PIS) as described with insulin-clamp techniques (SIGITmean). LIR and HIR displayed normal PIS and positive relationships versus exercise capacity. LIR's but not HIR's relative W(OBLA) was related to CS as earlier only documented in endurance athletes but at a lower level than in athletes. This pointed at a poor peripheral oxygen delivery in LIR. LIR's MQI decreased relative to HIR's the higher the muscle CS indicating radical related muscle trauma in LIR as in athletes. LIR representing prediabetes described muscle anomalies, which could represent prestages of the lesions observed in type-2 diabetes. They are claimed to be responsible for insulin-, glucose-, lipid-resistance, and peripheral circulatory resistance.
Mol Cell Biochem 1998 Jan
PMID:Muscle metabolism and quality (MQI) in prediabetic sedentary man. 954 83

Fatty acids are the preferred substrate of ischemic, reperfused myocardium and may account for the decreased cardiac efficiency during aerobic recovery. Neonatal cardiac myocytes in culture respond to hypoxia/serum- and glucose-free medium by a slow decline in ATP which reverses upon oxygenation. This model was employed to examine whether carnitine palmitoyltransferase I (CPT-I) modulates high rates of beta-oxidation following oxygen deprivation. After 5 h of hypoxia, ATP levels decline to 30% control values and CPT-I activity is significantly stimulated in hypoxic myocytes with no alteration in cellular carnitine content or in the release of the mitochondrial matrix marker, citrate synthase. This stimulation was attributed to an increase in the affinity of hypoxic CPT-I for carnitine, suggesting that the liver CPT-I isoform is more dominant following hypoxia. However, there was no alteration in hypoxic CPT-I inhibition by malonyl-CoA. DNP-etomoxiryl-CoA, a specific inhibitor of the liver CPT-I isoform, uncovered identical Michaelis kinetics of the muscle isoform in control and hypoxic myocytes with activation of the liver isoform. Northern blotting did not reveal any change in the relative abundance of mRNA for the liver vs. the muscle CPT-I isoforms. The tyrosine phosphatase inhibitor, pervanadate, reversed the hypoxia-induced activation of CPT-I and returned the affinity of cardiac CPT-I for carnitine to control. Reoxygenation was also associated with a return of CPT-I activity to control levels. The data demonstrate that CPT-I is activated upon ATP depletion. Lower enzyme activities are present in control and reoxygenated cells where ATP is abundant or when phosphatases are inhibited. This is the first suggestion that phosphorylation may modulate the activity of the liver CPT-I isoform in heart.
Mol Cell Biochem 1998 Mar
PMID:The liver isoform of carnitine palmitoyltransferase I is activated in neonatal rat cardiac myocytes by hypoxia. 954 43

We have investigated the effect of chronic exposure of rats to an hypoxic environment (10% O2; 3 weeks), on the first step of the intracellular energy transfer process in the myocardium, i.e. the transfer at mitochondrial level of high energy bonds from ATP to creatine. In the left ventricles from rats adapted to normobaric hypoxia, we observed, using the permeabilized fiber technique, that the stimulatory effect of creatine on the mitochondrial respiration in presence of a low ADP concentration (0.1 mM) was attenuated when compared to control. Furthermore, the creatine-induced decrease of the apparent K(m) for ADP of the mitochondrial respiration, which is observed in control, was significantly reduced. Both the basal and maximal respiratory rates of the fibers were unchanged by the hypoxic exposure of the rats. A significant decrease of the total creatine kinase activity from 755 to 630 IU/g wet weight (for control and hypoxic rats, respectively) was detected and was accompanied by a 25% decrease in mitochondrial isoform activity (mitoCK) and in the mitoCK/citrate synthase ratio. In the right ventricles, identical alterations in the effect of creatine on apparent K(m) for ADP were observed while we did not detect any changes in CK activity. The decrease in mitoCK activity and the fall in the reactivity of respiration to creatine could be interpreted as a mechanism for downregulating oxygen demand during chronic hypoxia. The consequences of such alterations on energy metabolism of cardiomyocytes under conditions of reduced oxygen supply are discussed.
J Mol Cell Cardiol 1998 Jul
PMID:Chronic exposure of rats to hypoxic environment alters the mechanism of energy transfer in myocardium. 971 Jul 98

We used the minitransposon TnhlyAs [Gentschev, I., Maier, G., Kranig, A. and Goebel, W. (1996) Mol. Gen. Genet. 252, 266-274] for random insertion of the secretion signal (HlyAs) of Escherichia coli hemolysin (HlyA) into chromosomal genes. Four mini-TnhlyAs derivatives bearing the gltA (citrate synthase), deoC (2 deoxyribose-5 phosphate aldolase), tig (trigger factor) genes and an unknown ORF fused to hlyAs were identified and characterized. Our data suggest that TnhlyAs-generated hemolysin fusion proteins are secreted efficiently by the HlyB/HlyD/TolC hemolysin secretion machinery and that this can be useful for studies of gene expression or function.
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PMID:Construction of chromosomally encoded secreted hemolysin fusion proteins by use of mini-TnhlyAs transposon. 971 56


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