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1

Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4  

UK PubMed Central (United Kingdom)

Mechanism-based inhibition of cytochrome P450 (CYP) 3A4 is characterized by NADPH-, time-, and concentration-dependent enzyme inactivation, occurring when some drugs are converted by CYPs to reactive...Full Text Available

2005-03-01

2

A cytochrome P450 terpenoid hydroxylase linked to the suppression of insect juvenile hormone synthesis  

UK PubMed Central (United Kingdom)

A cDNA encoding a cytochrome P450 enzyme was isolated from a cDNA library of the corpora allata (CA) from reproductively active Diploptera punctata cockroaches. This P450 from the endocrine...Full Text Available

1998-10-27

4

On the General Mechanism of Selective Induction of Cytochrome P450 Enzymes by Chemicals: Some Theoretical Considerations  

UK PubMed Central (United Kingdom)

Importance of the fieldThe cytochrome P450 (CYP) isoforms that are selectively induced following exposure to structurally-diverse chemicals often are the ones capable...Full Text Available

2010-04-01

5

Erratum to: Inhibition of triclabendazole metabolism in vitro by ketoconazole increases disruption to the tegument of a triclabendazole-resistant isolate of Fasciola hepatica  

British Library Electronic Table of Contents (United Kingdom)

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP 450) enzyme pathway was inhibited using ketoconazole (KTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 system was inhibited by a 2-h pre-incubation in ketoconazole (40??M), then incubated for a further 22?h in NCTC medium containing either KTZ, KTZ?+?nicotinamide adenine dinucleotide phosphate (NADPH) (1?nM), KTZ?+?NADPH?+?TCBZ (15??g/ml), or KTZ?+?NADPH?+?triclabendazole sulphoxide (TCBZ.SO; 15??g/ml). Changes to fluke ultrastructure following drug treatmen...

2011-01-01

6

The opposite effect of bivalent cations on cytochrome b5 reduction by NADH:cytochrome b5 reductase and NADPH:cytochrome c reductase.  

UK PubMed Central (United Kingdom)

The effects of bivalent cations on cytochrome b5 reduction by NADH:cytochrome b5 reductase and NADPH:cytochrome c reductase were studied with the proteinase-solubilized enzymes. Cytochrome b5 reduction...Full Text Available

1988-05-01

7

Clofibrate-induced cytochrome P450-lauric acid omega hydroxylase(P450LA omega):purification, cDNA cloning, sequence and regulation  

Energy Technology Data Exchange (ETDEWEB)

A cytochrome P450 that hydroxylates lauric acid at the 12 position (P450LA omega) was isolated from liver microsomes of clofibrate treated rats. P450LA omega was immunologically distinct from P450s a,b,c,d,e,f,g,h,j,PB1, and PCN1. Polyclonal antibody against P450LA omega was utilized to screen a gt11 cDNA library. A clone (pP450LA omega), was isolated and its sequence determined. The P450LA omega mRNA is a minimum 2387 nts in length and codes for a P450 of Mr.58,222 daltons. This protein shares less than 35% amino acid similarity with P450s b,c,d,e,f,PB1, and PCN1; however, it does contain a ...

1986-05-01

8

Determination of microsomal lauric acid hydroxylase activity by HPLC with flow-through radiochemical quantitation  

International Nuclear Information System (INIS)

An assay for the microsomal hydroxylation of lauric acid (LA), based on HPLC with flow-through radiochemical detection, has been developed. Conditions were optimized for resolution and quantitation of three microsomal metabolites of "1"4C-LA, one of which has not been reported previously as a metabolite of LA in mammalian microsomal incubations. These products, 12-(omega)-hydroxy-LA, 11-(omega-1)-hydroxy-LA, and a novel metabolite, 10-(omega-2)-hydroxy-LA, were isolated by HPLC and identified by gas chromatography/mass spectrometry. In the presence of NADPH, the formation of all three metabolites was linear with time and microsomal protein concentration. Hydrogen peroxide also supported the microsomal metabolism of LA, although the ratio of metabolites was substantially different than that produced by NADPH-supported microsomes. Several biochemical probes (metyrapone, #alpha#-naphthoflavone, 2-diethylaminoethyl-2,2-diphenylvalerate ...

9

Covalent Modification of Thr302 in Cytochrome P450 2B1 by the Mechanism-Based Inactivator 4-tert-Butylphenylacetylene  

UK PubMed Central (United Kingdom)

The mechanism of inactivation of cytochrome P450 2B1 (CYP2B1) by 4-tert-butylphenylacetylene (BPA) has been characterized previously to be caused by the covalent binding of a reactive...Full Text Available

2010-06-01

10

Induction of biotransformation in the liver of Eel (Anguilla anguilla L. ) by sublethal exposure to dinitro-o-cresol: An ultrastructural and biochemical study  

Energy Technology Data Exchange (ETDEWEB)

Structural and functional alterations in hepatocytes of the European eel, Anguilla anguilla, following a 4-week-exposure to 5, 50, and 250 micrograms/liter dinitro-o-cresol (DNOC) were investigated by means of electron microscopy and biochemistry and compared to liver pathology in eels exposed to the chemical spill into the Rhine river at Basle in November 1986. Whereas phenological parameters (growth, condition factor) are unaffected, ultrastructural and biochemical alterations are detectable at greater than or equal to 50 and 5 micrograms/liter DNOC, respectively. Structural modifications include: rounding-up of the nuclei; fractionation and reduction of the rough endoplasmic reticulum; proliferation of the smooth endoplasmic reticulum (SER), mitochondria, peroxisomes, and lysosomes; bundles of rod-shaped SER profiles; annulate lamellae; membrane whorls within mitochondria; crystallization of the peroxisomal matrix and glycogen bodies; glycogen depletion and lipid augmentation. ...

1991-04-01

11

Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome P450 genes  

UK PubMed Central (United Kingdom)

BackgroundTransposons, i.e. transposable elements (TEs), are the major internal spontaneous mutation agents for the variability of eukaryotic genomes. To address the general issue...Full Text Available

12

Protection against chemical-induced lung injury by inhibition of pulmonary cytochrome P-450.  

UK PubMed Central (United Kingdom)

Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P = S moiety of the thionates, of one or...Full Text Available

1990-04-01

13

Molecular basis of the inhibition of human aromatase (estrogen synthetase) by flavone and isoflavone phytoestrogens: A site-directed mutagenesis study.  

UK PubMed Central (United Kingdom)

Flavone and isoflavone phytoestrogens are plant chemicals and are known to be competitive inhibitors of cytochrome P450 aromatase with respect to the androgen substrate. Aromatase is the enzyme that...Full Text Available

1998-02-01

14

Induction of cytochrome P450 1A by cow milk-based formula: a comparative study between human milk and formula  

UK PubMed Central (United Kingdom)

During the treatment of neonatal apnea, formula-fed infants, compared to breastfed infants, show nearly three-fold increase in clearance of caffeine, a substrate...Full Text Available

2005-09-01

15

Preferential induction of cytochrome P450 1A1 over cytochrome P450 1B1 in human breast epithelial cells following exposure to quercetin  

British Library Electronic Table of Contents (United Kingdom)

Estrogen metabolism is suggested to play an important role in estrogen-induced breast carcinogenesis. Epidemiologic studies suggest that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Phytoestrogens are biologically active plant compounds that structurally mimic 17b-estradiol (E2). We hypothesize that phytoestrogens, may provide protection against breast carcinogenesis by altering the expression of estrogen-metabolizing enzymes cytochrome P450 1A1 (Cyp1A1) and 1B1 (Cyp1B1). Cyp1A1 and Cyp1B1 are responsible for the metabolism of E2 to generate 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2), respectively. Studies suggest that 2-OHE2 and 2-methoxyestradiol may protect against breast carcinogenesis, while 4-OHE2 is carcinogenic in rodent models....

2008-01-01

16

Altered lauric acid metabolism in renal microsomes from spontaneously hypertensive rats (SHR)  

International Nuclear Information System (INIS)

Studies investigated whether changes in omega- and (omega-1)-hydroxylation (OH) of lauric acid (LA) occurred in renal microsomes prepared from SHR compared to Wistar-Kyoto (WK) control rats. Systolic blood pressure in age-matched adult SHR and WKR were 189 +/- 3 and 123 +/- 4 mm Hg(anti X +/- SE) respectively (p < 0.001). No significant differences between SHR and WKR were seen in body weight, kidney weight or renal microsomal protein content. Renal microsomes, prepared from whole kidneys, were incubated with 10 mM NADPH and ["1"4C]LA at concentrations between 5-50 #mu#M. The 11- and 12-OH metabolites of LA were separated by HPLC using a reverse phase column with a methanol:water:acetic acid (62:37.8:0.2) mobile phase. Apparent (app) V/sub max/ values for 12-OH in WKR and SHR were 0.87 +/- 0.19 vs 1.48 +/- .11 nmoles/mg protein/min (p < 0.05), respectively, while values for 11-OH were 0.51 +/- 0.12 vs 0.60 +/- .07, respectively. No significant differences ...

1986-04-13

17

Myocardial pharmacokinetics of ebastine, a substrate for cytochrome P450 2J, in rat isolated heart  

British Library Electronic Table of Contents (United Kingdom)

BACKGROUND AND PURPOSE It is well established that cytochrome P450 2J (CYP2J) enzymes are expressed preferentially in the heart, and that ebastine is a substrate for CYP2J, but it is not known whether ebastine is metabolized in myocardium. Therefore, we investigated its pharmacokinetics in the rat isolated perfused heart. EXPERIMENTAL APPROACH Rat isolated hearts were perfused in the recirculating mode with ebastine for 130-min. The concentrations of ebastine and its metabolites, hydroxyebastine and carebastine, were measured using liquid chromatography with a tandem mass spectrometry. The data were analysed by a compartmental model. The time course of negative inotropic response was linked to ebastine concentration to determine the concentration-effect relationship. KEY RESULTS Ebastine w...

2011-01-01

18

Intravenous Formulation of HET0016 for Inhibition of Rat Brain 20-Hydroxyeicosatetraenoic Acid (20-HETE) Formation  

UK PubMed Central (United Kingdom)

N-Hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine (HET0016) is a potent inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) formation by specific cytochrome P450 (CYP) isoforms....Full Text Available

2008-11-01

19

Cyp1b1 exerts opposing effects on intestinal tumorigenesis via exogenous and endogenous substrates  

UK PubMed Central (United Kingdom)

Cytochrome P450 1B1 (Cyp1b1) metabolism contributes to physiological functions during embryogenesis, but also to carcinogenic activation of polycyclic aromatic hydrocarbons (PAH). We generated...Full Text Available

2008-09-15

20

ATF4 and the integrated stress response are induced by ethanol and cytochrome P450 2E1 in human hepatocytes  

British Library Electronic Table of Contents (United Kingdom)

Background & AimsMolecular mechanisms underlying alcoholic liver disease (ALD) are still not fully understood. Activating transcription factor-4 (ATF4) is the master coordinator of the integrated stress response (ISR), an adaptive pathway triggered by multiple stressors. which can promote cell death and induce metabolic dysregulation if the stress is intense or prolonged. The aim of this study was to assess the effect of alcohol on the ISR signaling pathway in human liver cells and to define the role of cytochrome P450 2E1 (CYP2E1) in this response. MethodsPrimary cultured human hepatocytes and human HepG2 cells over-expressing CYP2E1 by adenoviral infection were exposed to ethanol (25-100mM) for 8-48h. ResultsEthanol treatment of both liver cells up-regulated ATF4 as well as the pro-survi...

2011-01-01

 
 
 
 
21

One-electron reduction of chloroperoxidase by radiolytically generated electrons  

Energy Technology Data Exchange (ETDEWEB)

Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with {sup 60}Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.

1990-05-16

22

One-electron reduction of chloroperoxidase by radiolytically generated electrons  

International Nuclear Information System (INIS)

Upon irradiation of aqueous ethylene glycol/water solutions of native chloroperoxidase (CPO) with "6"0Co-gamma rays at 77K one observes the one-electron reduction of the enzyme active site by radiolytically generated thermolyzed electrons. In the present study the first absorption spectrum of a low-spin ferrous form of CPO is reported which has peaks at 438, 532 and 563 nm, similar to those observed previously for cytochrome P-450. All previously described ferrous forms of CPO are high spin. In order to observe the final results of the CPO reaction with electrons, the spectral changes of native enzyme after room temperature-gamma-irradiation have also been investigated. Evidence of changes is also presented probably connected with disruption of the tertiary structure of enzyme, correlated with decrease of enzyme activity.

1990-05-01

23

[mRNA level and cytochrome P450 1A activity in the liver of C57BL mice induced by various xenobiotics].  

Science.gov (United States)

The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was ...

24

Synthesis, characterization and biologic effects of polybrominated naphthalenes  

Energy Technology Data Exchange (ETDEWEB)

Although polybrominated naphthalenes (PBNs) are contaminants of the commercial fire retardant fireMaster BP-6, the individual PBN isomers have not been identified. In order to study PBNs possessing an analogous level of bromination to those found in fireMaster BP-6, three synthetic PBN mixtures, averaging 5.0, 5.3, and 5.6 bromines per naphthalene were synthetized and partially characterized. The PBN mixtures were administered to immature male Wistar rats and found to be potent inducers of cytochrome P-450-dependent monooxygenases. At the lowest dose tested, 30 mumol X kg-1, each PBN mixture caused maximal induction of benzo(a)pyrene hydroxylase activity. On the basis of enzyme activities, ligand-binding spectra and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the PBN mixtures were determined to be 3-methylcholanthrene-type inducers of cytochrome ...

1984-07-01

25

Zonal differences in DNA synthesis activity and cytochrome P450 gene expression in livers of male F344 rats treated with five nongenotoxic carcinogens  

Energy Technology Data Exchange (ETDEWEB)

Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a unique composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern ...

1995-12-31

26

Toxicity of ultraviolet-irradiated halothane in mice  

Energy Technology Data Exchange (ETDEWEB)

One such agent is the widely used anesthetic, halothane. To study the toxicity of u.v. decomposed halothane, mice were exposed to anesthetic concentrations (1.3%) of non- and u.v.-irradiated halothane in oxygen for 90 min. Halothane sleeping times increased from 14.3 min to 72.5 min. Microsomal mixed function oxidase activity decreased, as shown by prolonged pentobarbital sleeping times 1 day after exposure to halothane and irradiated halothane (54.6 min and 149.1 min, respectively, as compared to a 34.6-min control). Quantitative and qualitative differences were found in the amount of (/sup 14/C)-pentobarbital metabolites excreted by u.v. irradiated halothane-exposed mice compared to either oxygen or non-irradiated halothane-exposed groups. In addition, serum glutamic-oxalacetic transaminase (SGOT) of irradiated halothane-exposed mice increased to 233% of the control values, and serum glutamic-pyruvic transaminase (SGPT) were 377% of control values. No significant changes in SGOT or ...

1982-01-01

27

Systemic responses to inhaled ozone in mice: cachexia and down-regulation of liver xenobiotic metabolizing genes  

International Nuclear Information System (INIS)

Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we observed significant down-regulation of different families of mRNAs in the livers of the exposed mice, ...

2005-10-15

28

Enzyme induction in neonates after fetal exposure to antiepileptic drugs  

Energy Technology Data Exchange (ETDEWEB)

The /sup 13/C-AP breath test is shown to be a convenient, noninvasive method to monitor velocity and capacity of P450-dependent AP N-demethylation in infancy and childhood. According to /sup 13/C-AP breath tests, neonates have a very low capacity to eliminate /sup 13/CO/sub 2/, which is only 15 to 21% of the activity in adults. During the first year of life AP N-demethylation increases to reach its maximum at about 2 years; afterwards a slight decrease occurs. In 25 neonates exposed prenatally to different antiepileptic drugs /sup 13/C-AP breath test was efficiently used to prove that cytochrome AP N-demethylation was considerably stimulated. After primidone/phenobarbitone, especially in combination with phenytoin, /sup 13/C elimination reaches and even surpasses the range for older children. Valproate exposure during fetal life is not consistently followed by a significant increase in AP N-demethylation. The enzyme ...

1983-01-01

29

Attenuation by methyl mercury and mercuric sulfide of pentobarbital induced hypnotic tolerance in mice through inhibition of ATPase activities and nitric oxide production in cerebral cortex  

Energy Technology Data Exchange (ETDEWEB)

This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease ...

2008-06-15

30

Pyridine Nucleotide Specificity of Barley Nitrate Reductase 1  

UK PubMed Central (United Kingdom)

NADPH nitrate reductase activity in higher plants has been attributed to the presence of NAD(P)H bispecific nitrate reductases and to the presence of phosphatases capable of hydrolyzing NADPH to NADH....Full Text Available

1982-05-01

32

Disruption of contact inhibition in rat liver epithelial cells by various types of AhR ligands  

Energy Technology Data Exchange (ETDEWEB)

The maintenance of a balance between cell gain and cell loss is essential for proper liver function. The exact role of aryl hydrocarbon receptor (AhR) in regulating cell proliferation and apoptosis of liver cells remains unclear, since ligand-dependent activation of AhR has been shown to induce cell cycle arrest, proliferation, differentiation or apoptosis, depending on the cellular model used. AhR can directly interact with retinoblastoma protein in hepatic cells, forming protein complexes that can efficiently block cell cycle progression by inducing G1 arrest, or to induce the expression of inhibitors of cyclin-dependent kinases, such as p271. On the other hand, it has been suggested that AhR could play a stimulatory role in cell proliferation, either directly or by mediating a release from contact inhibition. It is now generally accepted that progenitor cells exist in the liver, are activated in various liver diseases and can form a potential target cell population for both tumor ...

2004-09-15

33

Soluble Epoxide Hydrolase Inhibition: Targeting Multiple Mechanisms of Ischemic Brain Injury with a Single Agent  

UK PubMed Central (United Kingdom)

SummarySoluble epoxide hydrolase (sEH) is a key enzyme in the metabolic conversion and degradation of P450 eicosanoids called epoxyeicosatrienoic acids (EETs). Genetic variations...Full Text Available

2009-03-01

34

Evolutionary history of a specialized P450 propane monooxygenase  

UK PubMed Central (United Kingdom)

SummaryThe evolutionary pressures that shaped the specificity and catalytic efficiency of enzymes can only be speculated. While directed evolution experiments show that new functions...Full Text Available

2008-11-28

35

The NADPH oxidase inhibitor diphenyleneiodonium is also a potent inhibitor of cholinesterases and the internal Ca2+ pump  

UK PubMed Central (United Kingdom)

Background and purpose:Diphenyleneiodonium (DPI) is often used as an NADPH oxidase inhibitor, but is increasingly being found to have unrelated side effects. We investigated its...Full Text Available

2009-10-01

36

Simultaneous activation of NADPH oxidase-related proton and electron currents in human neutrophils  

UK PubMed Central (United Kingdom)

Generation of reactive oxygen species by the NADPH oxidase complex is an important bactericidal weapon of phagocytes. Phorbol myristate acetate (PMA) is a potent agonist for this “respiratory...Full Text Available

2000-06-06

37

Soluble Variants of Rhodobacter capsulatus Membrane-anchored Cytochrome cy Are Efficient Photosynthetic Electron Carriers*  

UK PubMed Central (United Kingdom)

Photosynthetic (Ps) electron transport pathways often contain multiple electron carriers with overlapping functions. Here we focus on two c-type cytochromes (cyt) in facultative phototrophic...Full Text Available

2008-05-16

38

Reconstructing Mammalian Phylogenies: A Detailed Comparison of the Cytochrome b and Cytochrome Oxidase Subunit I Mitochondrial Genes  

UK PubMed Central (United Kingdom)

The phylogeny and taxonomy of mammalian species were originally based upon shared or derived morphological characteristics. However, genetic analyses have more recently played an increasingly important...Full Text Available

39

In vivo expression and mitochondrial targeting of yeast apoiso-1-cytochrome c fusion proteins.  

UK PubMed Central (United Kingdom)

To define the import pathway for apoiso-1-cytochrome c in vivo, the coding region for bacterial chloramphenicol acetyltransferase (CAT) or yeast copper metallothionein (CuMT) was fused to the carboxy...Full Text Available

1990-11-01

40

Cytochrome c-d regulates developmental apoptosis in the Drosophila retina  

UK PubMed Central (United Kingdom)

The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological...Full Text Available

2006-09-01

 
 
 
 
41

Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH  

UK PubMed Central (United Kingdom)

Increased oxidative stress is a known cause of cardiac dysfunction in animals and patients with diabetes, but the sources of reactive oxygen species [e.g., superoxide anion (O2)]...Full Text Available

2009-07-01

42

New Insights into Type II NAD(P)H:Quinone Oxidoreductases  

UK PubMed Central (United Kingdom)

Type II NAD(P)H:quinone oxidoreductases (NDH-2) catalyze the two-electron transfer from NAD(P)H to quinones, without any energy-transducing site. NDH-2 accomplish the turnover of NAD(P)H, regenerating...Full Text Available

2004-12-01

43

Distribution of NADPH-diaphorase activity in the central nervous system of the young and adult land snail Megalobulimus abbreviatus  

British Library Electronic Table of Contents (United Kingdom)

Nitric oxide (NO) is a gas produced through the action of nitric oxide synthase that acts as a neurotransmitter in the central nervous system (CNS) of adult gastropod mollusks. There are no known reports of the presence of NOS-containing neurons and glial cells in young and adult Megalobulimus abbreviatus. Therefore, NADPH-d histochemistry was employed to map the nitrergic distribution in the CNS of young and adult snails in an attempt to identify any transient enzymatic activity in the developing CNS. Reaction was observed in neurons and fibers in all CNS ganglia of both age groups, but in the pedal and cerebral ganglia, positive neurons were more intense than in other ganglia, forming clusters symmetrically located in both paired ganglia. However, neuronal NADPH-d activity in the mesocer...

2010-01-01

44

Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension  

Energy Technology Data Exchange (ETDEWEB)

Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible ...

1990-08-01

45

The Antibacterial Activity of Human Neutrophils and Eosinophils Requires Proton Channels but Not BK Channels  

UK PubMed Central (United Kingdom)

Electrophysiological events are of central importance during the phagocyte respiratory burst, because NADPH oxidase is electrogenic and voltage sensitive. We investigated the recent suggestion that...Full Text Available

2006-06-01

46

Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice  

UK PubMed Central (United Kingdom)

Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide...Full Text Available

2008-05-01

47

Charge compensation for NADPH oxidase activity in microglia in rat brain slices does not involve a proton current  

UK PubMed Central (United Kingdom)

The membrane properties of isolated cultured microglia have been extensively studied but it is important to understand their properties in situ, where they protect the brain against...Full Text Available

2008-09-01

48

A Hyperactive NAD(P)H:Rubredoxin Oxidoreductase from the Hyperthermophilic Archaeon Pyrococcus furiosus  

UK PubMed Central (United Kingdom)

NAD(P)H:rubredoxin oxidoreductase (NROR) has been purified from the hyperthermophilic archaeon Pyrococcus furiosus. The enzyme is exceedingly active in catalyzing the NADPH-dependent...Full Text Available

1999-09-01

49

Impaired mitochondrial energy metabolism and kinetic properties of cytochrome oxidase following acute aluminium phosphide exposure in rat liver  

British Library Electronic Table of Contents (United Kingdom)

The present study was designed with an aim to analyze the effect of acute aluminium phosphide (ALP) exposure (10mg/kg b.wt, intragastrically) on the kinetic characteristics of cytochrome oxidase and energy metabolism in male Wistar rat liver mitochondria. Liver mitochondrial preparations from ALP-treated rats exhibited significant decrease (66%) in the activity of cytochrome oxidase suggesting that there was a decrease in the catalytic efficiency of the active oxidase molecules on ALP treatment. The decreased activity of cytochrome oxidase with altered NADH and succinic dehydrogenase activities might have contributed towards a significant decline in state 3 and state 4 respiration as observed. These alterations in the electron transport chain complexes in turn adversely affected the ATP sy...

2010-01-01

50

Spectroscopic, Structural, and Functional Characterization of the Alternative Low-Spin State of Horse Heart Cytochrome c  

UK PubMed Central (United Kingdom)

The alternative low-spin states of Fe3+ and Fe2+ cytochrome c induced by SDS or AOT/hexane reverse micelles exhibited the heme group in a less...Full Text Available

2008-05-15

51

Release of oxidized plastocyanin from photosystem I limits electron transfer between photosystem I and cytochrome b6f complex in vivo  

UK PubMed Central (United Kingdom)

We used fast absorbance spectroscopy to investigate in vivo binding dynamics and electron transfer between plastocyanin (pc) and photosystem I (PSI), and cytochrome (cyt) f...Full Text Available

2005-05-10

52

Microsomal Electron Transfer in Higher Plants: Cloning and Heterologous Expression of NADH-Cytochrome b5 Reductase from Arabidopsis  

UK PubMed Central (United Kingdom)

AtCBR, a cDNA encoding NADH-cytochrome (Cyt) b5 reductase, and AtB5-A and AtB5-B, two cDNAs encoding Cyt b5, were isolated from Arabidopsis....Full Text Available

1999-01-01

53

Antioxidant properties of 4-methylcoumarins in in vitro cell-free systems  

British Library Electronic Table of Contents (United Kingdom)

4-Methylcoumarins that possess two hydroxyl groups ortho to each other in the benzenoid ring have shown to have excellent antioxidant and radical-scavenging properties in different experimental models. Furthermore, they cannot be metabolized by the liver P450 monoxygenases and thus cannot form 3,4-coumarin epoxides, which are believed to be mutagenic. Herein, we present a study on the structure activity relationship of eight synthetic 4-methylcoumarins, carried out by employing a series of different chemical cell-free tests. These compounds were tested by means of three assays involving one redox reaction with the oxidant (DPPH assay, ABTS+ assay and FRAP). Other assays were employed to evaluate the antioxidant properties of the coumarins under investigation against NO, O2- and HClO, which...

2010-01-01

54

Effect of paraquat on microsomal lipid peroxidation in vitro and in vivo. [Rats, rabbits, man, mice  

Energy Technology Data Exchange (ETDEWEB)

Rat lung and liver microsomes did not undergo lipid peroxidation in the absence of iron when incubated with NADPH and concentrations of paraquat ranging from 10/sup -7/ to 10/sup -2/ M. Paraquat also did not stimulate rat liver and lung microsomal peroxidation induced by added iron and NADPH, and was inhibitory at concentrations above 10 ..mu..M. Similarly, no stimulation of peroxidation was produced by paraquat in rabbit or human lung microsomes; however, under similar conditions, paraquat enhanced NADPH/iron-dependent peroxidation in mouse lung and liver microsomes obtained from rats sacrificed at 12, 18, and 24 hr following a lethal dose of paraquat (50 mg/kg, ip), there was no loss of vitamin E or increase in susceptibility to in vitro peroxidation which would be expected if lipid peroxidation had occurred in vivo although extensive lung damage developed during this time period. These results indicate that paraquat does ...

1980-01-01

56

Functional Characterization and Partial Purification of the Ubiquinol-Cytochrome c Oxidoreductase from Higher Plant Mitochondria (Helianthus tuberosus) 1  

UK PubMed Central (United Kingdom)

The functional and thermodynamic characteristics of the ubiquinolcytochrome (Cyt) c oxidoreductase in a Cyt b/c1-enriched fraction (defined...Full Text Available

1985-03-01

57

Enterococcus faecalis Heme-Dependent Catalase  

UK PubMed Central (United Kingdom)

Enterococcus faecalis cells cannot synthesize porphyrins and do not rely on heme for growth but can take up heme and use it to synthesize heme proteins. We recently described a cytochrome...Full Text Available

2002-11-01

58

Detection by /sup 125/I-cationized cytochrome c of proteoglycans and glycosaminoglycans immobilized on unmodified and on positively charged nylon 66  

Energy Technology Data Exchange (ETDEWEB)

We have examined the detection by a /sup 125/I-labeled basic protein, cationized cytochrome c, of selected proteoglycans (PGs) and standard preparations of glycosaminoglycans (GAGs) immobilized on Nylon 66 and also on positively charged Nylon 66. Immobilization on Nylon 66 appears to allow a relative freedom of interaction between PGs or GAGs and /sup 125/I-cationized cytochrome c, but a more restricted reaction was observed when PGs and GAGs were immobilized to positively charged Nylon 66. On this support PGs with large numbers of GAG side chains reacted well with /sup 125/I-cationized cytochrome c, but GAGs were minimally reactive. By taking advantage of some of the properties of large-pore agarose-acrylamide gels, rapid partial characterization of some PGs can be accomplished in the 10-ng range, and therefore at a sensitivity equal to PGs with internal biosynthetic labels.

1987-09-01

59

CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability  

UK PubMed Central (United Kingdom)

PurposeTo analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients.MethodsWe...Full Text Available

60

Synergistic Activation of Glucose-6-Phosphate Dehydrogenase and NAD(P)H oxidase by Src kinase Elevates Superoxide in Type 2 Diabetic, Zucker fa/fa, Rat Liver  

UK PubMed Central (United Kingdom)

Glucose metabolism through glycolysis and hexosamine pathway has been shown to be altered in type 2 diabetes. However, its fate through the pentose phosphate pathway (PPP) is currently unclear....Full Text Available

2009-08-01

 
 
 
 
61

NADPH oxidase-mediated reactive oxygen species production activates hypoxia-inducible factor-1 (HIF-1) via the ERK pathway after hyperthermia treatment  

UK PubMed Central (United Kingdom)

Hyperthermia (HT) is a strong adjuvant treatment with radiotherapy and chemotherapy because it causes tumor reoxygenation. However, the detailed molecular mechanisms of how HT enhances tumor oxygenation...Full Text Available

2010-11-23

62

Distinct Roles of Nox1 and Nox4 in Basal and Angiotensin II-Stimulated Superoxide and Hydrogen Peroxide Production  

UK PubMed Central (United Kingdom)

NADPH oxidases are major sources of superoxide (O2) and hydrogen peroxide (H2O2) in vascular cells. Production of these reactive oxygen species...Full Text Available

2008-11-01

63

Differential use of two cyclic electron flows around photosystem I for driving CO2-concentration mechanism in C4 photosynthesis  

UK PubMed Central (United Kingdom)

Whereas linear electron flow (LEF) in photosynthesis produces both ATP and NADPH, the cyclic electron flow (CEF) around photosystem I has been shown to produce only ATP. Two alternative routes have...Full Text Available

2005-11-15

64

Cotton plants expressing CYP6AE14 double-stranded RNA show enhanced resistance to bollworms  

British Library Electronic Table of Contents (United Kingdom)

RNA interference (RNAi) plays an important role in regulating gene expression in eukaryotes. Previously, we generated Arabidopsis and tobacco plants expressing double-stranded RNA (dsRNA) targeting a cotton bollworm (Helicoverpa armigera) P450 gene, CYP6AE14. Bollworms fed on transgenic dsCYP6AE14 plants showed suppressed CYP6AE14 expression and reduced growth on gossypol-containing diet (Mao et?al., in Nat Biotechnol 25: 1307?1313, 2007). Here we report generation and analysis of dsRNA-expressing cotton (Gossypium hirsutum) plants. Bollworm larvae reared on T2 plants of the ds6-3 line exhibited drastically retarded growth, and the transgenic plants were less damaged by bollworms than the control. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that the CYP6AE1...

2011-01-01

65

Structures of trihydroxynaphthalene reductase-fungicide complexes: implications for structure-based design and catalysis  

Energy Technology Data Exchange (ETDEWEB)

Trihydroxynaphthalene reductase catalyzes two intermediate steps in the fungal melanin biosynthetic pathway. The enzyme, a typical short-chain dehydrogenase, is the biochemical target of three commercial fungicides. The fungicides bind preferentially to the NADPH form of the enzyme. Three X-ray structures of the Magnaporthe grisea enzyme complexed with NADPH and two commercial and one experimental fungicide were determined at 1.7 {angstrom} (pyroquilon), 2.0 {angstrom} (2,3-dihydro-4-nitro-1H-inden-1-one, 1), and 2.1 {angstrom} (phthalide) resolutions. The chemically distinct inhibitors occupy similar space within the enzyme's active site. The three inhibitors share hydrogen bonds with the side chain hydroxyls of Ser-164 and Tyr-178 via a carbonyl oxygen (pyroquilon and 1) or via a carbonyl oxygen and a ring oxygen (phthalide). Active site residues occupy similar positions among the three structures. A buried water molecule that is ...

2010-03-08

66

Dimethoxycurcumin, a Structural Analogue of Curcumin, Induces Apoptosis in Human Renal Carcinoma Caki Cells Through the Production of Reactive Oxygen Species, the Release of Cytochrome c, and the Activation of Caspase-3  

UK PubMed Central (United Kingdom)

PurposeCurcumin (Cur) has been reported to induce apoptosis in human renal carcinoma Caki cells. Dimethoxycurcumin (DMC), one of several synthetic Cur analogues, has been reported...Full Text Available

2010-12-01

67

Detection by cationized /sup 125/I-cytochrome C of proteoglycans (PG) transferred to nylon  

Energy Technology Data Exchange (ETDEWEB)

Cytochrome c, labeled with /sup 125/I, has been used by us for staining glycosaminoglycans (GAG) separated by electrophoresis on cellulose acetate strips. As GAG between 1-10 ng could be quantified by autoradiography and densitometry, the reagent is approximately 100-fold more sensitive than currently used non-radiolabeled stains. The authors extend now the use of radiolabeled cytochrome c to the quantification of PG transblotted to solid supports subsequent to separation on polyacrylamine slab gels. Dot blotting used for exploring optimal conditions for detecting PG indicated that because of low background positively charged Nylon 66 was superior to nitrocellulose. Increasing the positive charge of the staining reagent by cationization decreased background radiation even further so that 1 ng PG could be seen readily after 5 hrs of autoradiography. Use of cationized /sup 125/I-cytochrome c has been made in detecting PG of ...

1986-05-01

68

Conformational Changes in BAK, a Pore-forming Proapoptotic Bcl-2 Family Member, upon Membrane Insertion and Direct Evidence for the Existence of BH3-BH3 Contact Interface in BAK Homo-oligomers*  

UK PubMed Central (United Kingdom)

During apoptosis, the pro-apoptotic Bcl-2 family proteins BAK and BAX form large oligomeric pores in the mitochondrial outer membrane. Apoptotic factors, including cytochrome c, are...Full Text Available

2010-09-10

69

Mechanisms of Reproductive Thermotolerance in Gossypium hirsutum: The Effect of Genotype and Exogenous Calcium Application  

British Library Electronic Table of Contents (United Kingdom)

Abstract Although photosynthetic thermotolerance has been investigated extensively in cotton leaves, reports on the biochemical influence of the pistil in promoting fertilization thermostability are limited. To evaluate the effect of temperature, genotype, and exogenous calcium application on fertilization and pistil biochemistry in cotton, thermosensitive (cv. ST4554 B2RF) and thermotolerant (cv. VH260) plants were grown under control (30/20-C) or high-temperature (38/20-C) conditions during flowering, and exogenous CaCl2 was applied to flowers 1-day prior to anthesis. Measured pistil parameters included fertilization efficiency; protein concentration; glutathione reductase, superoxide dismutase (SOD) and NADPH oxidase activities; and ATP and calcium levels. Exogenous calcium had no effec...

2011-01-01

70

Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli  

British Library Electronic Table of Contents (United Kingdom)

2-methylpropan-1-ol (isobutanol) is a leading candidate biofuel for the replacement or supplementation of current fossil fuels. Recent work has demonstrated glucose to isobutanol conversion through a modified amino acid pathway in a recombinant organism. Although anaerobic conditions are required for an economically competitive process, only aerobic isobutanol production has been feasible due to an imbalance in cofactor utilization. Two of the pathway enzymes, ketol-acid reductoisomerase and alcohol dehydrogenase, require nicotinamide dinucleotide phosphate (NADPH); glycolysis, however, produces only nicotinamide dinucleotide (NADH). Here, we compare two solutions to this imbalance problem: (1) over-expression of pyridine nucleotide transhydrogenase PntAB and (2) construction of an NADH-de...

2011-01-01

71

Distinguishing two groups of flavin reductases by analyzing the protonation state of an active site carboxylic acid  

British Library Electronic Table of Contents (United Kingdom)

Abstract Flavin-containing reductases are involved in a wide variety of physiological reactions such as photosynthesis, nitric oxide synthesis, and detoxification of foreign compounds, including therapeutic drugs. Ferredoxin-NADP(H)-reductase (FNR) is the prototypical enzyme of this family. The fold of this protein is highly conserved and occurs as one domain of several multidomain enzymes such as the members of the diflavin reductase family. The enzymes of this family have emerged as fusion of a FNR and a flavodoxin. Although the active sites of these enzymes are very similar, different enzymes function in opposite directions, that is, some reduce oxidized nicotinamide adenine dinucleotide phosphate (NADP+) and some oxidize reduced nicotinamide adenine dinucleotide phosphate (NADPH). In t...

2011-01-01

72

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes  

Energy Technology Data Exchange (ETDEWEB)

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a {lambda}gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu{sup 160}{yields}His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a {lambda}{sub max} at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 ...

1990-02-06

73

The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes  

International Nuclear Information System (INIS)

Three cDNAs, designated IIA3, IIA3v, and IIA4, coding for P450s in the CYP2A gene subfamily were isolated from a #lambda#gt11 library prepared from human hepatic mRNA. Only three nucleotide differences and a single amino acid difference, Leu"1"6"0#->#His, were found between IIA3 and IIA3v, indicating that they are probably allelic variants. IIA4 displayed 94% amino acid similarity with IIA3 and IIA3v. The three cDNAs were inserted into vaccinia virus, and recombinant viruses were used to infect human hepatoma Hep G2 cells. Only IIA3 was able to produce an enzyme that had a reduced CO-bound spectrum with a #lambda#_m_a_x at 450 nm. This expressed enzyme was able to carry out coumarin 7-hydroxylation and ethoxycoumarin O-deethylation. cDNA-expressed IIA3v and IIA4 failed to incorporate heme and were enzymatically inactive. Analysis of IIA proteins in human liver microsomes, using antibody against rat IIA2, revealed two proteins of 49 and 50 ...

1990-02-01

74

Gene expression profiles deciphering rice phenotypic variation between Nipponbare (Japonica) and 93-11 (Indica) during oxidative stress.  

Science.gov (United States)

Rice is a very important food staple that feeds more than half the world's population. Two major Asian cultivated rice (Oryza sativa L.) subspecies, japonica and indica, show significant phenotypic variation in their stress responses. However, the molecular mechanisms underlying this phenotypic variation are still largely unknown. A common link among different stresses is that they produce an oxidative burst and result in an increase of reactive oxygen species (ROS). In this study, methyl viologen (MV) as a ROS agent was applied to investigate the rice oxidative stress response. We observed that 93-11 (indica) seedlings exhibited leaf senescence with severe lesions under MV treatment compared to Nipponbare (japonica). Whole-genome microarray experiments were conducted, and 1,062 probe sets were identified with gene expression level polymorphisms between the two rice cultivars in addition to differential expression under MV treatment, which were assigned as Core Intersectional Probesets ...

2010-01-08

75

A novel chenodeoxycholic derivative HS-1200 induces apoptosis in human HT-29 colon cancer cells  

International Nuclear Information System (INIS)

To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile derivative (HS-1200). Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-19 cells were examined using a trypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. The dose required for the half maximal inhibition (IC_5_0) of the HT-29 cell growth was 100 #approx# 150 #mu# M of HS-1200. Several changes, associated with the apoptosis ...

2002-12-01

76

Specialized Circuits from Primary Visual Cortex to V2 and Area MT  

British Library Electronic Table of Contents (United Kingdom)

SummaryPrimary visual cortex recombines inputs from magnocellular (M) and parvocellular (P) streams to create functionally specialized outputs. Understanding these input-output relationships is complicated by the fact that layer 4B, which provides outputs to dorsal visual areas, contains multiple cell types. Using a modified rabies virus that expresses green fluorescent protein, we show that layer 4B neurons projecting to MT are a majority spiny stellate, whereas those projecting to V2 are overwhelmingly pyramidal. Regardless of cell type, MT-projecting neurons have larger cell bodies, more dendritic length, and are deeper within layer 4B. Furthermore, MT-projecting pyramidal neurons are located preferentially underneath cytochrome oxidase blobs, indicating that MT-projecting neurons of bo...

2007-01-01

77

Molecular prospecting for cryptic species in Phyllodistomum lacustri (Platyhelminthes, Gorgoderidae)  

British Library Electronic Table of Contents (United Kingdom)

Rosas-Valdez, R., Choudhury, A. & Prez-Ponce de Len, G. (2011). Molecular prospecting for cryptic species in Phyllodistomum lacustri (Platyhelminthes, Gorgoderidae). -Zoologica Scripta, 40, 296-305. Partial sequences of the 28S ribosomal RNA and cytochrome c oxidase I (COI) genes were compared among populations of a widely distributed and morphologically uniform digenean species in North America, Phyllodistomum lacustri, a parasite characteristically associated with ictalurid catfishes. Specimens were collected from the urinary bladder of ictalurid hosts in six localities of North America, spanning most of the latitudinal range of this freshwater fish group. Sequences of other congeneric species, including a potentially close relative, P.-staffordi, were also obtained and used for comparis...

2011-01-01

78

Molecular phylogeography of the microturbellarian Monocelis lineata (Platyhelminthes: Proseriata) in the North-East Atlantic  

British Library Electronic Table of Contents (United Kingdom)

Monocelis lineata is a complex of cryptic species (three in the Mediterranean and one in the Atlantic) widespread in midlittoral habitats. Throughout the range, populations with or without an ocular pigmented shield are found. We investigated the genetic structure of the North-East Atlantic populations with the aim of shedding light on their phylogeography and reconstructing possible patterns of recolonization after the Wrmian glaciation. Fourteen samples were investigated using cytochrome c oxidase subunit I (COI) and 13 by inter-simple sequence repeats (ISSRs). COI did not exhibit a clear pattern of decreased genetic diversity along a latitudinal gradient. Populations from Ferrol (Spain), Doolin (Ireland), and Helsingr (Denmark) showed a higher genetic variability, whereas a reduction in...

2011-01-01

79

Feeding ecology of Xenoturbella bocki (phylum Xenoturbellida) revealed by genetic barcoding  

British Library Electronic Table of Contents (United Kingdom)

Abstract The benthic marine worm Xenoturbella is frequently contaminated with molluscan DNA, which had earlier caused confusion resulting in a suggested bivalve relationship. In order to find the source of the contaminant, we have used molluscan sequences derived from Xenoturbella and compared them to barcodes obtained from several individuals of the nonmicroscopic molluscs sharing the same environment as Xenoturbella. Using cytochrome oxidase 1, we found the contaminating sequences to be 98% similar to the bivalve Ennucula tenuis. Using the highly variable D1-D2 region of the large ribosomal subunit in Xenoturbella, we found three distinct species of contaminating molluscs, one of which is 99% similar to the bivalve Abra nitida, one of the most abundant bivalves in the Gullmarsfjord where...

2008-01-01

80

6-Substituted imidazo[1,2-a]pyridines: Synthesis and biological activity against colon cancer cell lines HT-29 and Caco-2  

British Library Electronic Table of Contents (United Kingdom)

A range of 6-substituted imidazo[1,2-a]pyridines were synthesized using a multicomponent coupling reaction. Most of these compounds were found to exhibit excellent activity against the colon cancer cell lines HT-29 and Caco-2, whilst not showing significant toxicity against white blood cells. Our studies have shown that the proteolytic phase of apoptosis was initiated 2 h after treatment with these imidazo-[1,2-a]pyridines. The data suggests that the imidazo[1,2-a]pyridine-induced cell death in HT-29 and Caco-2 cells is mediated via pathway(s) that include the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase 3 and caspase 8.

2011-01-01

 
 
 
 
81

Some relationships between ultraviolet light and heme-protein-induced peroxidative lipid breakdown in liposomes, as reflected by fluorescence changes: the effect of negative surface charge  

International Nuclear Information System (INIS)

The water soluble, photolabile nitrene precursor, azidonaphthalene-2,7-disulfonic acid (ANDS) was encapsulated in small unilamellar, isoelectric (egg PC) or negatively charged (egg PC + dihexadecylphosphate) liposomes. The individual and combined effects of heme-proteins and UV irradiation on the fluorescence of these vesicles under aerobic conditions were studied. Consistent with the catalytic action of heme-proteins on lipid peroxidation and peroxide decomposition, addition of cytochrome c (positively charged) or catalase (negatively charged) to the vesicles elicited immediate formation of a fluorescence band at 470 nm, characteristic of Schiff bases that form from aldehyde byproducts of decomposing hydroperoxides. Ultraviolet irradiation of liposomes caused no significant changes in the fluorescence spectrum, in spite of the radiolysis of ANDS inside the vesicles with consequent formation of nitrene radicals. When isoelectric vesicles were irradiated with UV ...

82

Platinum(II) complexes as spectroscopic probes for biomolecules  

Energy Technology Data Exchange (ETDEWEB)

The use of platinum(II) complexes as tags and probes for biomolecules is indeed advantageous for their reactivities can be selective for certain purposes through an interplay of mild reaction conditions and of the ligands bound to the platinum. The use of {sup 195}Pt NMR as a method of detecting platinum and its interactions with biomolecules was carried out with the simplest model of platinum(II) tagging to proteins. Variable-temperature {sup 195}Pt NMR spectroscopy proved useful in studying the stereodynamics of complex thioethers like methionine. The complex, Pt(trpy)Cl{sup +}, with its chromophore has a greater potential for probing proteins. It is a noninvasive and selective tag for histidine and cysteine residues on the surface of cytochrome c at pH 5. The protein derivatives obtained are separable, and the tags are easily quantitated and differentiated through the metal-to-ligand charge transfer bands which are sensitive to the environment of the tag. ...

1990-09-21

83

Stable isotope studies on iron bio-availability in young Indian women: Effects of nutritional status, interactions and ethnicity  

International Nuclear Information System (INIS)

Iron is an essential micronutrient. As an integral part of hemoglobin, it is essential for the transport of oxygen in blood to the tissues. It is an important component of cytochromes and other tissue enzymes that are critical for cellular respiration and of myoglobin that helps maintain oxygen reserve in the muscle. It is also involved in the normal functioning of the immune function, and in the synthesis of steroid hormones and bile acids. There are serious functional consequences to iron deficiency and iron deficiency anemia (IDA) in the human body. The deleterious effects include increased morbidity, preterm delivery, low birth weight, delayed cognitive development, lowered cellular immunity and reduced physical work capacity. However, iron deficiency and IDA remain the world's most common deficiency disease in the 21st century. Recent estimates of people affected with iron deficiency and IDA are 3.5 billion. Iron deficiency anemia is most prevalent and severe ...

2002-06-24

84

Morusin induces apoptosis and suppresses NF-#kappa#B activity in human colorectal cancer HT-29 cells  

International Nuclear Information System (INIS)

Morusin is a pure compound isolated from root bark of Morusaustralis (Moraceae). In this study, we demonstrated that morusin significantly inhibited the growth and clonogenicity of human colorectal cancer HT-29 cells. Apoptosis induced by morusin was characterized by accumulation of cells at the sub-G_1 phase, fragmentation of DNA, and condensation of chromatin. Morusin also inhibited the phosphorylation of IKK-#alpha#, IKK-#beta# and I#kappa#B-#alpha#, increased expression of I#kappa#B-#alpha#, and suppressed nuclear translocation of NF-#kappa#B and its DNA binding activity. Dephosphorylation of NF-#kappa#B upstream regulators PI3K, Akt and PDK1 was also displayed. In addition, activation of caspase-8, change of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO, and activation of caspase-9 and -3 were observed at the early time point. Downregulation in the expression of Ku70 and XIAP was exhibited afterward. Caspase-8 or wide-ranging ...

2008-07-18

85

Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy : a rapid diagnostic method for studying cellular responses to stress and disease.  

Energy Technology Data Exchange (ETDEWEB)

We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions ...

2006-12-01

86

Phytoremediation of Ionic and Methyl Mercury P  

Science.gov (United States)

Our long-term goal is to enable highly productive plant species to extract, resist, detoxify, and/or sequester toxic heavy metal pollutants as an environmentally friendly alternative to physical remediation methods. We have focused this phytoremediation research on soil and water-borne ionic and methylmercury. Mercury pollution is a serious world-wide problem affecting the health of human and wild-life populations. Methylmercury, produced by native bacteria at mercury-contaminated wetland sites, is a particularly serious problem due to its extreme toxicity and efficient biomagnification in the food chain. We engineered several plant species (e.g., Arabidopsis, tobacco, canola, yellow poplar, rice) to express the bacterial genes, merB and/or merA, under the control of plant regulatory sequences. These transgenic plants acquired remarkable properties for mercury remediation. (1) Transgenic plants expressing merB (organomercury lyase) extract methylmercury from their growth substrate and ...

1999-06-01