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

Addition of vanadate, stimulated oxidation of NADH by rat liver microsomes. The products were NAD+ and H2O2. High rates of this reaction were obtained in the presence of phosphate buffer and at low pH values. The yellow-orange colored polymeric form of vanadate appears to be the active species and both ortho- and meta-vanadate gave poor activities even at mM concentrations. The activity as measured by oxygen uptake was inhibited by cyanide, EDTA, mannitol, histidine, ascorbate, noradrenaline, adriamycin, cytochrome c, Mn2+, superoxide dismutase, horseradish peroxidase and catalase. Mitochondrial outer membranes possess a similar activity of vanadate-stimulated NADH oxidation. But addition of mitochondria and some of its derivative particles abolished the microsomal activity. In the absence of oxygen, disappearance of NADH measured by decrease in absorbance at 340 nm continued at nearly the same rate since vanadate served as an electron acceptor in the microsomal system. Addition of excess catalase or SOD abolished the oxygen uptake while retaining significant rates of NADH disappearance indicating that the two activities are delinked. A mechanism is proposed wherein oxygen receives the first electron from NAD radical generated by oxidation of NADH by phosphovanadate and the consequent reduced species of vanadate (Viv) gives the second electron to superoxide to reduce it H2O2. This is applicable to all membranes whereas microsomes have the additional capability of reducing vanadate.
Mol Cell Biochem 1987 Jun
PMID:Vanadate-stimulated NADH oxidation in microsomes. 365 Jun 94

Indole-3-carbinol (I-3-C) was examined for its ability to protect mice against 24-hr N-nitrosodimethylamine (NDMA)-mediated hepatotoxicity. NDMA (20 mg/kg body weight) alone produced extensive hemorrhagic and centrolobular necrotic lesions, with a necrotic severity index of 3.0 +/- 0.4 (scale of 0-5). Treatment with 50 mg/kg body weight of I-3-C by gavage, 1 hr prior to NDMA, substantially protected against hemorrhagic lesions. Furthermore, I-3-C lowered the NDMA-mediated tissue necrotic index to 1.5 +/- 0.3, by reducing the extent of tissue necrosis rather than the severity in the necrotic region. Release of liver enzymes into the blood correlated with the histopathology; I-3-C reduced NDMA-mediated elevated activities of plasma alanine transaminase and ornithine transcarbamylase by 84 and 51.3%, respectively. Although no changes in nonprotein sulfhydryls were evident at 24-hr after NDMA, ascorbate levels were reduced to 40% of control values. However, treatment with I-3-C prior to NDMA prevented the decline in tissue ascorbate concentrations. In vitro, I-3-C was found to be a type II ligand for cytochrome P-450, with a Ks value of 237 microM. However, if such binding occurs in vivo, it does not protect against the approximately 60% decrease in hepatic cytochrome P-450 or the 80% decrease in NDMA demethylase I activity produced by NDMA. Since I-3-C slightly enhances cytochrome P-450 content and NDMA demethylase activity, the histopathologic protection by I-3-C must be due to factors other than inhibiting metabolic activation of NDMA.
Exp Mol Pathol 1987 Oct
PMID:Protection from N-nitrosodimethylamine-mediated liver damage by indole-3-carbinol. 365 48

We have demonstrated in rat adrenal (Natarajan, R.D. and Harding, B.W. (1985) J. Biol. Chem. 260, 3902-3905) that NADH-semidehydroascorbate reductase and ascorbate participate in an electron transport pathway (ETP) supplying reducing equivalents from NADH to cytochrome P-450scc. Here, we demonstrate that this ascorbate dependent ETP also supplies reducing equivalents to cytochrome P-450(11 beta/18) in both rat adrenal and bovine adrenal cortex. The activity is dependent upon addition of catalase or upon 'cold shock' treatment of isolated mitochondria. Comparison of the rates of 11 beta- and 18-hydroxylation supported by this ETP and by the classical pathway supported by various TCA cycle intermediates suggests that in vivo the ascorbate dependent pathway may be essential for maximal flow of reducing equivalents to the mitochondrial hydroxylases. Partial reconstitution of the ascorbate dependent 11 beta/18-hydroxylase activity was achieved with purified bovine outer mitochondrial and inner mitochondrial membranes fortified with supernatant from sonified mitochondria all preincubated with phosphatidyl choline. These preparations no longer require catalase or 'cold shock' treatment. Ascorbate and NADH-semidehydroascorbate reductase are unable to support 17 alpha- or 21-hydroxylase activity in isolated bovine adrenal cortical microsomes whether incubated with purified outer mitochondrial membranes or not.
Mol Cell Endocrinol 1987 Sep
PMID:The function of NADH-semidehydroascorbate reductase and ascorbic acid in corticosteroid hydroxylation. 366 95

The effects of the microtubular inhibitor, podophyllotoxin, on mitochondrial respiration were determined using isolated, digitonin-permeabilized hepatocytes and isolated mitochondria. In hepatocytes, podophyllotoxin (1.5 mM) inhibited coupled and uncoupled respiration of both FAD and NAD-linked substrates. In mitochondria, podophyllotoxin inhibited State III respiration, prevented the return to State IV respiration, and inhibited uncoupled respiration. There was no inhibition of ascorbate/TMPD oxidation in either the hepatocytes or the mitochondria. Podophyllotoxin had no effect upon oligomycin inhibition of coupled respiration. Oligomycin had no effect on the podophyllotoxin-inhibition of uncoupled respiration in either hepatocytes or mitochondria. The results indicate that podophyllotoxin alters electron flow at a site early in the electron transport chain.
Mol Cell Biochem 1986 Jun
PMID:Inhibition of respiration in mitochondria and in digitonin-treated rat hepatocytes by podophyllotoxin. 372 50

Although electrical field stimulation has been used to evoke neural responses in blood vessels this technique can also generate activated oxygen molecules which may affect the experimental preparation. We evaluated this by stimulating 10 cc of aerated Krebs-Henseleit solution for a period of 20 s and then transferring the fluid to a pre-contracted segment of bovine pulmonary artery. The parameters required to achieve 50% maximal relaxation were a voltage of 4.0 +/- 0.3 volts (mean +/- S.E.), a frequency of 1.6 +/- 0.1 Hz and a pulse duration of 0.37 +/- 0.02 ms. Exposure to stimulated fluid caused greater amounts of relaxation in vessels pre-contracted with serotonin than in those pre-contracted with either histamine or potassium chloride. Relaxation was not endothelial dependent and it was not inhibited by adrenergic or cholinergic blockade. Since both ascorbate and catalase but not superoxide dismutase inhibited relaxation, it appears that hydrogen peroxide is involved. We conclude that even low intensity electrical field stimulation generates activated oxygen molecules in oxygenated physiologic buffer solution and that these molecules can relax blood vessels both directly and by altering the response to drugs in the muscle bath. These effects must be considered when using electrical field stimulation to study blood vessels.
J Mol Cell Cardiol 1986 Sep
PMID:Activated oxygen molecules generated by electrical stimulation affect vascular smooth muscle. 378 31

Ascorbic acid uptake in AtT-20 tumor cells and primary cultures of rat anterior and intermediate pituitary was sodium-dependent and showed half-maximal saturation between 9 and 18 microM ascorbate. When incubated in [14C]ascorbic acid at concentrations similar to those in serum (50 microM), all of the cells concentrated ascorbate 20- to 40-fold, producing intracellular ascorbate concentrations of 1-2 mM. HPLC analyses showed that over 90% of the intracellular label comigrated with authentic ascorbic acid. Although ascorbate was rapidly oxidized in culture medium in the absence of cells, incubation of ascorbate in culture medium in the presence of cells stabilized the ascorbate substantially. Unlike systems that transport dehydroascorbic acid, the ascorbate transport systems in all three preparations were not inhibited by glucose. Thus all three systems possess similar saturable, high-affinity, sodium-dependent active transport systems for ascorbic acid.
Mol Cell Endocrinol 1986 Dec
PMID:Transport and stability of ascorbic acid in pituitary cultures. 380 8

Phosphorylating mitochondrial membranes were obtained from Trypanosoma cruzi culture (epimastigote) forms. Using ADP as phosphate acceptor and succinate, sn-glycerol-3-phosphate, L-malate or ascorbate plus tetramethyl-p-phenylenediamine (TMPD) as oxidizable substrates, energy coupling sites II and III were detected, with respiratory control values in the range of 2.8-2.0. Carbonyl cyanide m-chlorophenylhydrazone and sonication uncoupled the respiratory control mechanism. Antimycin and cyanide partially inhibited succinate, sn-glycerol-3-phosphate and L-malate oxidation, while cyanide totally inhibited ascorbate + TMPD oxidation by the mitochondrial preparation. Succinate oxidation was inhibited by malonate and oxalacetate, but this latter was only effective with sonicated mitochondria. At variance with other substrates, NADH oxidation was not controlled by ADP concentration or inhibited by antimycin or cyanide. Rotenone failed to inhibit electron transfer in T. cruzi mitochondria.
Mol Biochem Parasitol 1985 Sep
PMID:Respiratory control in mitochondria from Trypanosoma cruzi. 390 95

Phosphorylating mitochondrial preparations were obtained from T. cruzi culture (epimastigote) forms by grinding the cells with glass - beads and differential centrifugation. Using ADP as phosphate acceptor and succinate, L-malate or ascorbate + tetramethyl-p-phenylenediamine (TMPD) as oxidizable substrates, the respiratory control (R.C.) values were (mean +/- S.D.; n = 4, in parenthesis, the substrate): 2.8 +/- 0.10 (succinate): 2.3 +/- 0.13 (L-malate) and 2.0 +/- 0.12 (ascorbate + TMPD). The ADP:O values were 1.68 +/- 0.08, 1.42 +/- 0.08 and 0.66 +/- 0.66 +/- 0.12, respectively. The uncoupler CCCP stimulated substrate oxidation somewhat more than ADP. Succinate oxidation was by malonate and also by oxaloacetate but the latter was effective only after sonicating the mitochondrial preparation. The mitochondrial membranes oxidized also NADH but this oxidation was not subjected to control by the phosphate acceptor. Our results support the existence of two energy-conserving sites in T. cruzi respiratory chain (sites 2 and 3) and confirm previous observations by Stoppani et al. (Mol. Biochem. Parasitol. 2:3-21, 1980) with intact epimastigotes.
 ...
PMID:[Existence of 2 sites of oxidative phosphorylation in Trypanosoma cruzi]. 391 70

Mitochondria isolated from tissues of hypoxic animals have increased respiratory capacity (State 3 respiration) when assayed in vitro at ambient oxygen tensions. The present study utilized the isolated perfused rat heart to determine whether or not this change could be produced in the absence of the neural and hormonal changes that accompany hypoxia in vivo. Following 10-min single pass retrograde perfusion with normoxic Krebs-Henseleit buffer (PO2 greater than or equal to 600 mmHg), perfusion was continued for up to 15 min with either normoxic or hypoxic buffer (PO2 less than or equal to 150 mmHg). After 10 min of hypoxic perfusion State 3 respiration of the mitochondria from the hypoxic hearts was 13 to 15% higher (P less than or equal to 0.05) than that of normoxic hearts when assayed with either glutamate/malate or succinate as substrate but was unchanged when TMPD and ascorbate was the substrate. Succinate-supported State 4 respiration of the hypoxic mitochondria also showed a small (10%) but significant (P less than or equal to 0.05) increase. These changes were not abolished by preperfusing the heart with propranolol (10(-7), 10(-6), or 10(-5) M) indicating that the response was not attributable to release of local stores of catecholamines. Respiratory control and ADP/O ratios as well as contents of cytochrome c and aa3 of the mitochondria from the hypoxic hearts were similar to those of normoxic hearts indicating that the mitochondria remained intact and tightly coupled. We concluded that the hypoxia-induced increase in mitochondrial State 3 respiration, while independent of neural and hormonal influences from the body requires an intracellular event, since they cannot be reproduced by subjecting isolated mitochondria to hypoxia in vitro.
J Mol Cell Cardiol 1985 Jan
PMID:Mitochondrial respiration following acute hypoxia in the perfused rat heart. 398 72

The average rate of endogenous respiration of intact Litomosoides carinii was 2.24 muatom O min-1 g-1 worm wet wt. No significant difference was observed in respiration capacities between male and female worms. Rates of oxygen uptake decreased progressively during disruption and fractionation of the parasite tissue and very few respiration capabilities remained in the mitochondrial fraction. Added substrates increased the respiratory rates of the intact filariid and cell-free extracts by a factor of 1.4 to 2.3, depending on the tissue system and substrate species used. Rotenone and cyanide strongly inhibited respiration in all incubations, whereas antimycin A, in most cases, suppressed oxygen consumption only partially. ATP conservation in cell-free extracts of L. carinii, as determined by the incorporation of 32Pi into the organic phosphate fraction, was twice as high in the presence of air as under an atmosphere of nitrogen. Anaerobically, rates of phosphorylation in these extracts were similar to the amounts of lactate. Phosphorylation in mitochondria isolated from the filarial worm was supported by malate, succinate, pyruvate and TMPD/ascorbate, whereas L-glutamate and beta-hydroxybutyrate exhibited only little or no effect, respectively. P/O ratios for pyruvate-supported oxidative phosphorylation were found to approach a value of 3. Electron transport inhibitors, oligomycin and 2,4-dinitrophenol strongly inhibited substrate-dependent mitochondrial phosphorylation. The data of the present investigation, together with other recent findings made by the same authors, have provided evidence that in L. carinii mitochondria a mammalian-type of respiratory system capable of carrying out oxidative phosphorylation is functional. It seems likely that this respiration-dependent chemical energy, proceeding in addition to that generated through fermentation processes, may be vital for muscular contraction and survival of this filarial parasite.
Mol Biochem Parasitol 1985 Apr
PMID:Respiration and energy conservation in the filarial worm Litomosoides carinii. 399 Jul 8


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