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At least 613 records · Page 34Linked to original sources
PubMed1982

Effects of pH, CO2 and organic phosphates on oxygen affinity of sea turtle hemoglobins.

The affinities of adult-type hemoglobins of green (Chelonia mydas) and loggerhead (Caretta caretta) sea turtles were determined at 25.7 degrees C as a function of pH, PCO2 and each of the organic phosphates found in erythrocytes of these species (ATP, IHP (substitute for IPP) and DPG). Each species showed a single hemoglobin band in cellulose acetate electrophoresis which isoelectric focusing resolved into one major and three minor components having isoelectric points near pH 7.2. Oxygen binding curves were recorded using a modified 'Hemoscan' (Instrument Division, Travenol Laboratories, Savage, MD). Hemolysates were kept saturated with CO during preparation to prevent methemoglobin formation. CO was driven off immediately before performing each oxygen binding determination, using the photodissociative effect of the Hemoscan light beam. In both species, phosphate-free hemoglobin has higher affinity than whole blood, and had lower pH sensitivity. CO2 (37 Torr) reduces affinity, particularly in the green sea turtle, and eliminates pH sensitivity. Each organic phosphate tested reduces affinity, with IHP being most effective at a given concentration and DPG least effective. Organic phosphates are most effective at low pH, and restore both pH sensitivity and oxygen affinity to whole-blood levels taking into account the difference between plasma and intracellular pH. Reasons are suggested why the organic phosphate effect was not detected in a previous study. Hemolysates of both species are distinctive in giving upward-curving Hill plots, with n = 1 asymptotes at low saturation that are insensitive to pH, CO2 and organic phosphates. The oxygen affinities corresponding to these asymptotes are about 100 Torr in both species. Results are compared to oxygen dissociation curves obtained from whole blood.

Animals↗
PubMed2003

Positron emission tomographic imaging of angiogenesis and vascular function.

Surrogate markers of clinical outcome are important in anticancer drug research, since clinical criteria of response develop only slowly and may be confounded by other processes than drug effect. The need for surrogate outcome markers is especially great with newer agents that may act by tumour stabilization as opposed to shrinkage. Neoplastic angiogenesis is associated with a number of detectable changes at molecular and microcirculatory levels. Therefore, direct study of angiogenic molecular biology and tumour circulation before during and after treatment may offer useful surrogate markers for vascular-targeted therapies. The main advantage of radiotracer imaging with positron emission tomography (PET) is its functional specificity. This article will review two main areas: (a) the methodology behind PET imaging of tumour blood supply with 15O-oxygen labelled compounds; and (b) newer tracers in development as markers of angiogenetic biology.

Cell Hypoxia↗
PubMed2001

Cyclodextrin dimers as cleavable carriers of photodynamic sensitizers.

Several phthalocyanines carrying hydrophobic components have been synthesized and shown to bind to a group of cyclodextrin dimers with a carbon-carbon double bond in the linker. The complexes are soluble in water. On irradiation in the presence of oxygen, the singlet oxygen produced cleaves the olefinic linkers in the complexes, resulting in precipitation of the sensitizers. This process concentrates the sensitizers in the light beam, a process that has useful potential in photodynamic therapy.

Cyclodextrins↗
PubMed1999

Biochemical characterization of human S-nitrosohemoglobin. Effects on oxygen binding and transnitrosation.

S-Nitrosation of cysteine beta93 in hemoglobin (S-nitrosohemoglobin (SNO-Hb)) occurs in vivo, and transnitrosation reactions of deoxygenated SNO-Hb are proposed as a mechanism leading to release of NO and control of blood flow. However, little is known of the oxygen binding properties of SNO-Hb or the effects of oxygen on transnitrosation between SNO-Hb and the dominant low molecular weight thiol in the red blood cell, GSH. These data are important as they would provide a biochemical framework to assess the physiological function of SNO-Hb. Our results demonstrate that SNO-Hb has a higher affinity for oxygen than native Hb. This implies that NO transfer from SNO-Hb in vivo would be limited to regions of extremely low oxygen tension if this were to occur from deoxygenated SNO-Hb. Furthermore, the kinetics of the transnitrosation reactions between GSH and SNO-Hb are relatively slow, making transfer of NO+ from SNO-Hb to GSH less likely as a mechanism to elicit vessel relaxation under conditions of low oxygen tension and over the circulatory lifetime of a given red blood cell. These data suggest that the reported oxygen-dependent promotion of S-nitrosation from SNO-Hb involves biochemical mechanisms that are not intrinsic to the Hb molecule.

Allosteric Regulation↗
PubMed1994

Screening of unsubstituted cyclic compounds as inhibitors of monoamine oxidases.

A number of unsubstituted aromatic hydrocarbons, azaheterocycles, oxaheterocycles and cyclic ketones were screened for their inhibitory potency towards monoamine oxidases (MAO; EC 1.4.3.4.) A and B. Fair activities (IC50 10-100 microM) and selectivities were found for, e.g. naphthalene, anthracene, phenanthrene, isoquinoline and acridine. The most active inhibitors are oxygen-containing compounds (e.g. coumarin, flavone, dibenzofuran, xanthene, thioxanthone and acridone), with xanthone emerging as a potent (IC50 0.8 microM) and reversible MAO-A inhibitor. All tested inhibitors seem to act in a reversible and time-independent manner.

Animals↗
PubMed1981

EPR spectral changes of nitrosyl hemes and their relation to the hemoglobin T-R transition.

EPR spectra of nitrosyl hemes were used to study the quaternary structure of hemoglobin. Human adult hemoglobin has been titrated with nitric oxide at pH 7.0 and 25 degrees C. After the equilibration of NO among the alpha and beta subunits the samples were frozen for EPR measurements. The spectra were fitted by linear combinations of three standard signals: the first arising from NO-beta-hemes and the other two arising for NO-alpha-hemes of molecules in the high- and low-affinity conformations. The fractional amounts of alpha subunits exhibiting the high-affinity spectrum fitted the two-state model (Edelstein, S.J. (1974) Biochemistry 13, 4998-5002) with the allosteric constant L = 7.10(6) and relative affinities cNO alpha and cNO beta approx. 0.01. Hemoglobin has been marked with nitric oxide one chain using low-saturation amounts of nitric oxide. The EPR spectra was studied as a function of oxygen saturation. Linear combinations of the three standard signals above fitted these spectra. The fractions of molecules exhibiting the high-affinity spectrum fitted the two-state model with L = 7 . 10(6), c)2 = 0.0033 and cNO alpha = 0.08, instead of cNO alpha = 0.01. Thus, the two-state model is not adequate to describe the conformational transition of these hybrids. The results present evidence of the non-equivalence between oxygen and nitric oxide as ligands.

Adult↗
PubMed2004

Control of oxygen atom chirality and chelate ring conformation by protected/free sugar hydroxyl groups in glucose-pendant dipicolylamine-copper(II) complexes.

A pair of copper(II) complexes 1 and 2 exhibit an enantiomeric chiral center at the oxygen atom that coordinates to the metal center. The configurations of the oxygen atom chirality and the chelate ring conformation are simply controlled by protected/free hydroxyl groups of the sugar moiety, yielding mirror image CD spectra. In this system, repulsive and attractive forces are used to regulate chirality on the copper-coordinated oxygen atom both in the solid state and in solution.

Copper↗
PubMed1988

Opposite effects of WR-2721 and WR-1065 on radiation-induced hypothermia: possible correlation with oxygen uptake.

Ionizing radiation induces hypothermia in guinea pigs. While systemic injection of the radioprotectant S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) did not block hyperthermia induced by exposure to 10 Gy of gamma radiation, central administration did attenuate it. The dephosphorylated metabolite of WR-2721, N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065), accentuated radiation-induced hypothermia by both routes of administration. In brain homogenates, oxygen uptake was inhibited by WR-2721 but elevated by WR-1065. These results suggest that the antagonism of radiation-induced hypothermia found only after central administration of WR-2721 is due to its direct actions and not to its dephosphorylated metabolite and that this effect may be correlated with the inhibition by WR-2721 of oxygen uptake.

Amifostine↗
PubMed1991

Antitumor agents. 120. New 4-substituted benzylamine and benzyl ether derivatives of 4'-O-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II.

A number of new 4'-O-demethylepipodophyllotoxin derivatives possessing various 4 beta-N- or 4 beta-O-benzyl groups have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The 4 beta-N-benzyl derivatives 9-22 are, in general, as active or more active than etoposide (1). The most active compounds are 14, 16, and 17, which are more than 2-fold more potent than 1. The results indicated that a basic unsubstituted 4 beta-benzylamino moiety is structurally required for the enhanced activity. Replacement of the benzyl nitrogen with oxygen gave compounds (23 and 24) which are inactive. The ability of these compounds to inhibit human DNA topoisomerase II and to cause protein-linked DNA breakage appears to have no direct correlation with cytotoxicity in KB cells.

Enzyme Inhibitors↗
PubMed1995

Intraphagosomal oxygen in stimulated macrophages.

A new electron paramagnetic resonance (EPR)-based method was developed to obtain selective information on pO2 in a specific intracellular compartment (phagosomes). This method did not require the use of a broadening agent thereby eliminating one of the potential sources of experimental error with EPR oximetry. An oxygen-sensitive probe (4-(Trimethylammonium) 2,2,6,6-tetramethylpiperidine-d17-1-oxyl iodide (d-Cat1)) which has a net positive charge, was incorporated selectively into the phagosomes of macrophages stimulated with zymosan. Extracellular oxygen was measured by addition of a neutral nitroxide (4-oxo-2,2,6,6-tetramethylpiperidine-d16-1-oxyl (15N PDT)) to this same sample. Measurements based on EPR linewidths showed the average intraphagosomal oxygen concentration to be 11.2 +/- 3.4 microM lower than that measured from the extracellular compartment when the sample was perfused with air, and this was increased on stimulation of mitochondrial consumption or by increasing the oxygen concentration in the extracellular compartment. These experiments provide what we believe to be the first reported measurements of the oxygen concentration in a specific intracellular location (intraphagosomal) and its comparison with the oxygen concentration in the extracellular space. The observed gradient cannot be explained in terms of known coefficients of diffusion, and these results are consistent with previous reports that a gradient in oxygen concentration can occur between the average intracellular and extracellular concentration of oxygen.

Animals↗
PubMed1984

Effects of triethyllead chloride on hepatic microsomal N- and C-oxygenation of N,N-dimethylaniline in rats.

Triethyllead chloride was added directly to male rat liver microsomes (0.0, 0.05, 0.25, 0.5, 1.0, and 3.0 mM), or the rats were pretreated with ip injections, once a day for 2 days (0.0, 1.5, and 3.0 mg triethyllead chloride/kg body wt), and microsomes prepared without any further treatment on Day 3. The effects of these treatments on microsomal N-oxygenation and C-oxygenation in vitro were studied by using N-oxide formation and N-demethylation of N,N-dimethylaniline (DMA) as test reactions. Increased microsomal N-oxygenation was obtained by in vivo treatment and decreased microsomal C-oxygenation by in vitro treatment. As a result, either treatment thus gave rise to an increase in the N-oxygenation/C-oxygenation ratio. Conditions favoring accumulation of the N-oxide product may potentiate the tumor-inducing characteristics of carcinogenic aromatic amines.

Aniline Compounds↗