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At least 343 records · Page 19Linked to original sources
PubMed2000

NF- kappa B independent suppression of endothelial vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 gene expression by inhibition of flavin binding proteins and superoxide production.

Oxidation-reduction (redox) coupled mechanisms play an important role in the regulation of cell surface adhesion molecule expression. In endothelial cells membrane-bound NADH/NADPH oxidase is a significant source of intracellular superoxide (O(2)(-)) production. We explored the role of flavin containing proteins such as NADH/NADPH oxidase in the induction of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) gene expression in human aortic endothelial cells (HAECs) and human dermal microvascular endothelial cells (HMECs). Treatment of HAECs by tumor necrosis factor- alpha (TNF- alpha, 100 U/ml) for 1 h induced a 31% increase in O(2)(-)production within 5 min as determined by lucigenin chemiluminescence analysis of whole cells (n=4, P<0.05). Pretreatment with the NADH/NADPH oxidase inhibitor diphenylene iodonium (DPI, 40 microm) for 1 h inhibited O(2)(-)production. DPI also inhibited TNF and LPS-induced VCAM-1 and ICAM-1 cell surface expression and TNF- alpha, LPS, or IL-1 beta induced VCAM-1 and ICAM-1 mRNA accumulation. However, DPI did not inhibit TNF- alpha -induced activation of nuclear NF- kappa B-like binding activity in HAECs and HMECs. Furthermore, DPI did not inhibit TNF- alpha induced transactivation of NF- kappa B-driven VCAM-1 and HIV-LTR promoter gene constructs in transiently transfected HMECs. These data suggest that flavin binding proteins such as NADH/NADPH oxidase can regulate VCAM-1 gene expression independent of NF- kappa B. Furthermore, intracellular O(2)(-)generation is not necessary for NF- kappa B activation or for transactivation of NF- kappa B driven promoters.

Aorta↗
PubMed1998

Inhibition of hypoxic pulmonary vasoconstriction in isolated rat pulmonary arteries by diphenyleneiodonium (DPI).

The NADPH oxidase inhibitor, diphenyleneiodonium (DPI), is known to selectively inhibit hypoxic pulmonary vasoconstriction (HPV) in isolated rat and rabbit lungs. We have investigated whether DPI has similar effects in rat pulmonary arteries in vitro. Vessels (n=38, internal diameters 327+/-41 microM) were mounted in an automated myograph and preconstricted with prostaglandin F2alpha (PGF2alpha, 5 microM) before an acute hypoxic challenge. The effects of DPI (10 microM), or the vehicle DMSO, were studied on the first contractile phase of HPV. DPI (10 microM) was found to significantly inhibit HPV; 1.83+/-0.42 mN/mm (pre-DPI) compared to 0.11+/-0.22 mN/mm (post-DPI,P<0.01). However, the vehicle DMSO (0.2%) also resulted in a reduction of HPV, although this was significantly different from inhibition via DPI (P<0.05), implying a DPI-sensitive component. The effects of DPI (0.1-300 microM) were also studied on the second contractile phase of HPV. DPI (300 microM) caused a significant reversal of 45% (0.50-0.27 mN/mm) compared to 9% reversal (0.38-0.35 mN/mm) seen with DMSO (P<0.0001). The fact that an inhibitor of NADPH oxidase, the enzyme responsible for producing reactive oxygen species from oxygen, attenuated the pulmonary vascular response to hypoxia, may indicate that this, or a similar, enzyme is involved in oxygen sensing.

Animals↗
PubMed2000

The effects of aliphatic (n-nonane), naphtenic (1,2, 4-trimethylcyclohexane), and aromatic (1,2,4-trimethylbenzene) hydrocarbons on respiratory burst in human neutrophil granulocytes.

This study investigates the effects of aliphatic (n-heptane, n-nonane), naphtenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)), and aromatic (methylbenzene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on respiratory burst in human granulocytes. The free radical formation was measured as 2,7-dichlorofluorescein diacetate-amplified (DCF) fluorescence, by electron paramagnetic resonance (EPR) spectroscopy and by hydroxylation of 4-hydroxybenzoate. The chemotactic peptide N-formyl-met-leu-phe (fMLP) and phorbol 12-myristate 13-acetate (PMA), a diacylglycerol analogue, were included as positive controls. DCF fluorescence was elevated in a concentration-dependent manner by C9 hydrocarbons. The C7 hydrocarbons did not stimulate respiratory burst in the concentration range examined. The naphtenic hydrocarbon TMCH showed the strongest effect on respiratory burst and was therefore selected for mechanistic studies of this free radical formation. In the absence of extracellular Ca(2+), fluorescence in response to TMCH and fMLP was reduced by 77 and 90%, respectively. Preincubation of the granulocytes with the protein kinase C inhibitor bisindolylmaleimide reduced the DCF fluorescence stimulated with TMCH, fMLP, and PMA by 82, 56, and 90%, respectively. The phospholipase C inhibitor U73122 lowered the TMCH- and fMLP-activated DCF fluorescence by 87 and 76%. In addition, the TMCH- and fMLP-induced DCF fluorescence, after the preincubation with the phospholipase D modulator n-butanol, was lowered by 83 and 52%, respectively. The importance of protein kinase C, phospholipase C, and phospholipase D for elevation of respiratory burst was also demonstrated by the EPR experiments using the spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). Preincubation with the NADPH oxidase inhibitor diphenyleneiodonium and diethyldithiocarbamate, which inhibits superoxide dismutase, led to an almost complete reduction of DCF fluorescence in response to TMCH, fMLP, and PMA. Preincubation with diethyldithiocarbamate led to the elevation of superoxide adducts of DEPMPO. The hydrocarbons stimulated formation of mainly the superoxide (O(*-)(2)) adduct of DEPMPO (DEPMPO-OOH) but also small amounts of the hydroxyl adduct ((*)OH) (DEPMPO-OH). Using 4-hydroxybenzoate as a hydroxyl radical trap confirmed formation of (*)OH after stimulation with the hydrocarbons. In conclusion, our findings indicate that TMCH-activated respiratory burst is dependent on the Ca(2+)-dependent phospholipase C, phospholipase D, and protein kinase C prior to activation of the NADPH oxidase.

1-Butanol↗
PubMed1994

Oxidants act as chemorepellents in Paramecium by stimulating an electrogenic plasma membrane reductase activity.

Paramecium is a valuable eukaryotic model system for studying chemosensory transduction, adaptation and cellular sensory integration. While millimolar amounts of many attractants hyperpolarize and cause faster forward swimming, oxidants are repellents that depolarize and cause backward swimming at micromolar concentrations. The non-permeant oxidants cytochrome c, nitro blue tetrazolium and ferricyanide are repellents with half maximal concentrations of 0.4 microM, 2.2 microM and 100 microM respectively. In vivo reductase activities follow the same order of potencies. The concentration dependence of the cytochrome c reductase activity is well correlated with cytochrome c-induced depolarizations. This suggests that plasma membrane reduction of external cytochrome c is electrogenic, causing membrane depolarization and chemorepulsion. The reductase activity also appears to be voltage dependent. Depolarization by either K+, Na+, Ca++ or Mg++ correlates with inhibition of both in vivo reductase activities and cytochrome c-induced membrane potential changes. These responses were also seen in deciliated cells, showing that the body plasma membrane is sufficient for the response. Both chloroquine and diphenyleneiodonium inhibited reductase activities but only at unusually high concentrations. This activity showed no pH dependence in the physiological range. We propose that a plasma membrane bound NA-DPH-dependent reductase controls oxidant-induced depolarizations and consequent chemorepulsion.

Animals↗
PubMed1984

Transmembrane signal defect and absence of cancer extract induced leukocyte adherence inhibition (LAI) for leukocytes from patients with advanced cancer.

Leukocytes from patients with early cancer exhibit leukocyte adherence inhibition (LAI) when incubated with extracts of cancer of the same organ and histogenesis, whereas leukocytes from patients with advanced cancer seldom do. To understand the reason for this refractory state, tumor antigen-induced LAI and transmembrane signalling were measured in the same leukocytes. Transmembrane signalling was measured by changes in membrane potential (delta psi) by the [3H]tetraphenylphosphonium equilibration technique. When leukocytes from patients with early breast cancer were incubated with extracts of breast cancer and malignant melanoma they showed delta psi changes consisting of depolarization and hyperpolarization beginning within 0.5 min after addition of the breast cancer extract and finishing 15 min later. Moreover, they showed no delta psi changes when incubated with extracts of normal breast tissue. Leukocytes from subjects without cancer seldom showed delta psi changes. In criss-cross experiments, leukocytes from patients with melanoma only exhibited delta psi changes when incubated with the melanoma extract. There was a strong correlation between cancer extract-induced delta psi change and LAI. The delta psi change was triggered by leukotriene-like mediators from antibody-dependent monocytes. Authentic leukotrienes triggered delta psi changes in all subpopulation of leukocytes. Leukocytes from patients with advanced breast cancer when incubated with breast cancer extract did not transmit a signal or show LAI. Brief elevation of intracellular cyclic AMP restored both delta psi change and LAI induced by breast cancer extracts, indicating that reactive leukocytes are present but in a refractory state. We conclude that leukocytes from patients with advanced cancer do not react in LAI because tumor antigen does not trigger a transmembrane signal to initiate the cascade of biochemical reactions and physiological changes for LAI.

Breast Neoplasms↗
PubMed1992

Effects of inhibitors of ion-motive ATPases on the plasma membrane potential of murine erythroleukemia cells.

The membrane electric effects of N,N'-dicyclohexyl-carbodiimide (DCCD) and vanadate were studied in murine erythroleukemia cells (MELC), comparing the patch-clamp technique and the accumulation ratio (ARexp) of [3H]-tetraphenylphosphonium (TPP+). Electrophysiological measurements showed that both these inhibitors produce, at micromolar concentrations, a 20-30 mV hyperpolarization of resting potential (delta psi p) of MELC, which is abolished when the electrochemical equilibrium potential of K+ (EK) is brought close to zero. DCCD and vanadate turned out to have distinct targets on the plasma membrane of MELC (an H+ pump and the Na+,K(+)-ATPase, respectively). Measurements of ARexp showed that: (i) patch-clamp measurements of delta psi p were equivalent to those based on ARexp of antimycin-pretreated cells (ARANT); (ii) DCCD produced a strong increase in ARANT, that was antagonized by carbonyl cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) and diethylstilbestrol (DES); (iii) vanadate determined a marked increase in ARANT that was insensitive to FCCP, but antagonized by ouabain; (iv) incubation in high K+ medium (HK) brought ARANT to 1.0 in the controls, but did not lower this ratio below 3.0 in the presence of DCCD or vanadate; (v) the total amount of TPP+ taken up by the cells was in any case water extractable by a freezing and thawing procedure. On the whole, our data indicate that DCCD and vanadate hyperpolarize the MELC by increasing the K+ conductance and, at the same time, enhance the TPP+ binding, probably by changing the electrostatic potential profile of the plasma membrane. These effects seem to involve functional modifications of the target pumps, apparently related to the ion-occluding state of these enzymes.

Adenosine Triphosphatases↗
PubMed1986

Use of 11C-triphenylmethylphosphonium for the evaluation of membrane potential in the heart by positron-emission tomography.

The membrane potential in cells can be estimated by electrophysiological techniques and biomedical methods using lipophilic cations labelled with 14C. However, these techniques cannot be applied to the human heart. In this study a lipophilic cation, triphenylmethylphosphonium (TPMP), was labelled with carbon-11 with the purpose of investigating its suitability for the estimation of membrane potential in vivo. A biodistribution study in mice and rats showed significant uptake of the cation in the heart a few minutes after IV injection which remained constant for 60 min. In vivo study by positron-emission tomography showed that after IV injection of 11C-TPMP in the dog, activity rose almost immediately in the myocardium and then remained constant for 60 min. A rapid injection of KCl (greater than 40 mg/kg) 20 min after injection of 11C-TPMP led to an instantaneous fall in myocardial 11C-TPMP concentration. Membrane potential (delta psi), calculated from the TPMP distribution ratio between intracellular and plasma water space by the Nernst equation, was estimated at -148.1 +/- 6.0 mV for the dog heart. This value reflected both cell membrane potential and mitochondrial membrane potential and, thus, the energy state of the myocardial cells.

Animals↗
PubMed1992

Protonmotive force in freshwater sulfate-reducing bacteria, and its role in sulfate accumulation in Desulfobulbus propionicus.

The protonmotive force in several sulfate-reducing bacteria has been determined by means of radiolabelled membrane-permeant probes (tetraphenylphosphonium cation, TPP+, for delta psi, and benzoate for delta pH). In six of ten freshwater strains tested only the pH gradient could be determined, while the membrane potential was not accessible due to nonspecific binding of TPP+. The protonmotive force of the other four strains was between -110 and -155 mV, composed of a membrane potential of -80 to -140 mV and a pH gradient between 0.25 and 0.8 (inside alkaline) at pH(out) = 7. In Desulfobulbus propionicus the pH gradient decreased with rising external pH values. This decrease, however, was compensated by an increasing membrane potential. Sulfate, which can be highly accumulated by the cells, did not affect the protonmotive force, if added in concentrations of up to 4 mM. The highest sulfate accumulation observed (2500-fold), which occurred at external sulfate concentrations below 5 microM, could be explained by a symport of three protons per sulfate, if equilibrium with the protonmotive force was assumed. At higher sulfate concentrations the accumulation decreased and suggested an electroneutral symport of two protons per sulfate. At sulfate concentrations above 500 microM, the cells stopped sulfate uptake before reaching an equilibrium with the protonmotive force.

Gram-Negative Anaerobic Bacteria↗
PubMed1992

Modulation of rat olfactory bulb mitochondrial function by atrial natriuretic peptide.

Atrial Natriuretic Peptide (ANP) and receptors for ANP are widely distributed in many tissues and cell types in vertebrates. ANP has been shown to be internalized into the cytoplasm in several cell types and thus it raises the possibility that it may act on intracellular receptors. Displacement experiments of [125I]-ANP binding to rat olfactory bulb mitochondrial fraction demonstrated the presence of high affinity (Kd < 10(-9)M) binding sites (Bmax, 112 fmol/mg protein) in this preparation. The addition of ANP (10(-8) M) to this mitochondrial preparation resulted in a 25% increase in TPP+ accumulation, signifying a striking hyperpolarization of the mitochondrial membrane. In contrast ANP did not increase TPP+ uptake to liver mitochondrial preparations. This direct effect of ANP on Olfactory bulb mitochondrial membrane potential may underly the known effects of this hormone on steroidogenesis.

Animals↗
PubMed1983

Proton translocation during denitrification by a nitrifying--denitrifying Alcaligenes sp.

A heterotrophic nitrifying Alcaligenes sp. from soil was grown as a denitrifier on nitrate and subjected to oxidant pulse experiments to ascertain the apparent efficiencies of proton translocations during O2 and nitrogen-oxide respirations. With endogenous substrate as the reducing agent the leads to H+/2e- ratios, extrapolated to zero amount of oxidant per pulse, were 9.4, 3.7, 4.3 and 3.5 for O2, nitrate, nitrite and N2O, respectively. The value for O2 and those for the N-oxides are, respectively, somewhat larger and smaller than corresponding values for Paracoccus denitrificans. None of the three permeant ions employed with the Alcaligenes sp. (valinomycin-K+, thiocyanate and triphenylmethylphosphonium) was ideal for all purposes. Thiocyanate provided highest ratios for O2 but abolished the oxidant pulse response for nitrate and N2O. Valinomycin was slow to penetrate to the cytoplasmic membrane and relatively high concentrations were required for optimal performance. Triphenylmethylphosphonium enhanced passive proton permeability and diminished proton translocation at concentrations required to realize the maximal oxidant pulse response.

Alcaligenes↗
PubMed1983

Action and binding of palytoxin, as studied with brain membranes.

Palytoxin in concentrations as low as 10(-11) to 10(-12) M promotes the outflow of the lipophilic [3H]tetraphenylphosphonium ion from particulate brain cortex of guinea-pigs and rats, and from preloaded crude synaptosomes of rats, which indicates depolarization. The outflow is not influenced by tetrodotoxin or the calcium channel blocker nimodipin, or by substitution of choline for Na+ ions. It is increased by Ca2+ and by borate, the latter interacting with the toxin itself. To assess the fixation of palytoxin to biological membranes, a binding step was installed before the depolarization step. Palytoxin binds to membranes from rat brain, liver, kidney, human and dog erythrocytes, and to a lesser degree to liposomes made from rat brain or erythrocyte lipids. Binding is reversible. It is decreased by mild physical pretreatments of crude synaptosomes. Palytoxin binding is increased in the presence of micromolar concentrations of Ca2+ or borate. It is concluded that the potentiation of palytoxin actions by Ca2+ or borate is at least partially due to the promotion of its binding.

Acrylamides↗