Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of pure calf-liver and Escherichia coli thioredoxin reductases decreased drastically in the presence of NADPH or NADH, while NADP+, NAD+ and oxidized E. coli thioredoxin activated both enzymes significantly, particularly the bacterial one. The loss of activity under reducing conditions was time-dependent, thus suggesting an inactivation process: in the presence of 0.24 mM NADPH the half-lives for the E. coli and calf-liver enzymes were 13.5 and 2 min, respectively. Oxidized E. coli thioredoxin fully protected both enzymes from inactivation, and also promoted their complete reactivation after only 30 min incubation at 30 degrees C. Lower but significant protection and reactivation was also observed with NADP+ and NAD+. EDTA protected thioredoxin reductase from NADPH inactivation to a great degree, thus indicating the participation of metals in the process; EGTA did not protect the enzyme from redox inactivation. Thioredoxin reductase was extensively inactivated by NADPH under aerobic and anaerobic conditions, thus excluding the participation of O2 or oxygen active species in redox inactivation. The loss of thioredoxin reductase activity promoted by NADPH was much faster and complete in the presence of NAD+ glycohydrolase, thus suggesting that inactivation was related to full reduction of the redox-active disulfide. Those results indicate that thioredoxin reductase activity can be modulated in bacteria and mammals by the redox status of NADP(H) and thioredoxin pools, in a similar way to glutathione reductase. This would considerably expand the regulatory potential of the thioredoxin-thioredoxin reductase system with the enzyme being self-regulated by its own substrate, a regulatory protein.
Mol Cell Biochem 1992 Jan 15
PMID:NADPH and oxidized thioredoxin mediate redox interconversion of calf-liver and Escherichia coli thioredoxin reductase. 131 49

We investigated the susceptibility of sarcolemmal Na+K(+)-ATPase to singlet oxygen. The role of this enzyme is regulation of Na+ concentration and thereby membrane potential. Inhibition of Na+ pump would lead to intracellular Ca2+ overload therefore further aggravating the injury caused by free radicals. Incubation of isolated sarcolemmal vesicles with irradiated rose bengal (150 nM) resulted in 86 +/- 1% inhibition of Na+K(+)-ATPase activity and histidine (25-100 mM) protected the enzyme in a dose-dependent fashion whereas SOD, catalase or mannitol (.OH radical scavenger) did not have any effect. Also, the inhibition of Na+K(+)-ATPase activity was dependent on rose bengal concentration, intensity of irradiation, duration of light exposure, showing that inhibition was directly related to amount of singlet oxygen generated. These results show that singlet oxygen may have significant disruptive effects on sarcolemmal function and may represent an important mechanism by which the oxidative injury to the myocardium induces arrhythmogenesis.
J Mol Cell Cardiol 1992 May
PMID:Singlet oxygen-induced inhibition of cardiac sarcolemmal Na+K(+)-ATPase. 132 12

Oxygen free radicals (OFRs) have been suggested in the pathogenesis of Parkinson's disease (PD). These free radicals exert their cytotoxic effect by peroxidation of lipid membrane resulting in the formation of malondialdehyde (MDA). Polymorphonuclear (PMN) leukocyte is one of the major sources of OFR. However, the oxygen free radical producing activity of PMN leukocytes in patients with PD is not known. We therefore studied the oxygen free radical producing activity of polymorphonuclear leukocytes and MDA levels in the serum of healthy subjects and in patients with Parkinson's disease. The oxygen free radical producing activity of PMN leukocytes in blood and the MDA content in serum were significantly higher in patients with Parkinson's disease than in healthy subjects. These results indicate a possible role of oxygen free radicals in the pathogenesis of Parkinson's disease.
Mol Cell Biochem 1992 Jun 26
PMID:Oxygen free radical producing activity of polymorphonuclear leukocytes in patients with Parkinson's disease. 132 91

The growth factors that operate while the lung remodels in hyperoxia are not known. At the lung periphery, high oxygen levels cause cell hypertrophy and hyperplasia, and this results in a thickening of the alveolar-capillary membrane and the walls of its associated microvessels. The present study examines gene expression of platelet-derived growth factor (PDGF) receptor and its ligand in this region of the lung of rats breathing 87% oxygen and compares this with the levels of expression in normal lung. In similar peripheral lung tissue, the proliferative response of specific cell populations has been assessed by [3H]thymidine incorporation and autoradiography. Normal lung expresses PDGF alpha-receptor subunit transcripts of 6.5 and 4.7 kb and PDGF beta-receptor transcripts of 5.5 and 4.5 kb. PDGF A-chain transcripts of 2.9, 2.3, and 1.7 kb are also expressed, each being at 10-fold higher levels than the single 3.5-kb transcript detected for PDGF B-chain. Within hours of breathing high concentrations of oxygen, mRNA levels change rapidly for the PDGF receptor subunits. These levels return to normal after 1 day and then decline over the next 28 days of exposure. PDGF A-chain mRNA increases 12 to 18 h after exposure, but then returns to normal levels. It is the PDGF B-chain mRNA that responds most to hyperoxia by increasing 10-fold on day 3. This increase immediately precedes the proliferative response on day 4 of microvascular adventitial fibroblasts, precursor smooth muscle cells, and epithelial cells but not smooth muscle cells, which do not proliferate until day 28.
Am J Respir Cell Mol Biol 1992 Sep
PMID:Differential regulation of the genes encoding platelet-derived growth factor receptor and its ligand in rat lung during microvascular and alveolar wall remodeling in hyperoxia. 132 10

The effects of chronic hypoxia on isolated neonatal rat cardiac myocytes were investigated in a model system of myocardial hypoxia. Spontaneously beating myocardiocytes were cultured for up to one week inside an environmental chamber at an oxygen tension of between 4 and 8 mmHg. In order to stimulate a chronic reduced flow condition fresh hypoxic culture medium was replenished frequently to eliminate or minimize contributions of extracellular metabolite build-up, pH changes, or energy depletion. Under these conditions contractions became progressively impaired and irregular compared with aerobic cultures and beating frequency decreased to about 50% of control over 3 days. Reduced contractility was paralleled by a progressive decrease in the basal intracellular level of cAMP. Both of these effects could be reversed by introducing isoproterenol. Visualization of calcium fluxes using the fluorescent calcium chelator Indo-1 demonstrated that the slower contractions were associated with a pronounced decrease in the rate of calcium efflux during muscle relaxation. Changes in the expression of cAMP dependent genes was apparent in the hypoxic cells and the chronic administration of cAMP elevating drugs was toxic specifically to cells under hypoxia. We propose that cAMP may regulate some short and long-term adaptations of cardiac myocytes to chronic hypoxia.
J Mol Cell Cardiol 1992 Jul
PMID:Molecular regulation of cardiac myocyte adaptations to chronic hypoxia. 132 57

Lidocaine, a local anaesthetic, has been shown to reduce ventricular arrhythmias associated with myocardial infarction and ischemic myocardial injury and its protective effects has been attributed to its membrane stabilizing properties. Since oxygen radicals are known to be produced during ischemia induced tissue damage, we have investigated the possible antioxidant properties of lidocaine and found that lidocaine does not scavenge O2-. radicals at 1 to 20 mM concentrations. However, lidocaine was found to be a potent scavenger of hydroxyl radicals and singlet oxygen. Hydroxyl radicals were produced in a Fenton type reaction and detected as DMPO-OH adducts by electron paramagnetic resonance spectroscopic techniques. Lidocaine inhibited DMPO-OH adduct formation in a dose dependent manner. The amount of lidocaine needed to cause 50% inhibition of that rate was found to be approximately 80 microM and at 300 microM concentration it virtually eliminated the DMPO-OH adduct formation. The production of OH.-dependent TBA reactive products of deoxyribose was also inhibited by lidocaine in a dose dependent manner. Lidocaine was also found to inhibit the 1O2-dependent 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO) formation in a dose dependent manner. 1O2 was produced in a photosensitizing system using Rose Bengal or Methylene Blue as photosensitizers and was detected as TEMP-1O2 adduct by EPR spectroscopy. The amount of lidocaine required to cause 50% inhibition of TEMP-1O2 adduct formation was found to be 500 microM. These results suggest that the protective effect of lidocaine on myocardial injury may, in part, be due to its reactive oxygen scavenging properties.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1992 Oct 07
PMID:Lidocaine: a hydroxyl radical scavenger and singlet oxygen quencher. 133 38

The purpose of this study was to determine whether an early increase in [Ca2+]i preceding generalized lysis of cardiomyocytes occurred during photodynamic permeabilization. A method was developed which facilitated the simultaneous measurement, in real time, of permeabilization of the sarcolemma to Ca2+ and Mn2+ during photodynamic action. Quin-2 loaded cells were illuminated in the presence of erythrosin B and the change in the fluorescence emission of the calcium-quin-2 complex was used to measure the rate and extent of change in [Ca2+]i. The same system was used in the presence of extracellular Mn2+ to determine how quickly the cardiomyocytes became permeable to either Mn2+ or quin-2. Calcium ions were observed to enter the myocytes prior to permeabilization of the sarcolemma to either Mn2+ or quin-2, and thus before membrane lysis. Lysis of cardiomyocytes did not appear to be dependent upon increases in [Ca2+]i. Controls were performed to rule out fluorescent artifacts. Reperfusion injury and photodynamic therapy involve both the production of free radicals and an early increase in [Ca2+]i. This study demonstrates a direct correlation between the production of reactive oxygen species and prelytic increases in [Ca2+]i in neonatal cardiomyocytes and demonstrates that this phenomenon may be common to many cell types.
J Mol Cell Cardiol 1992 Oct
PMID:Intracellular calcium during photodynamic permeabilization of cardiomyocytes. 133 59

Rate constants of 8-oxy-dGMP (8-hydroxy-dGMP) formation upon incubating dGMP in H2O solutions at different temperatures were determined with differential UV-spectroscopy. Extrapolation of rate constant values obtained at elevated temperatures to 37 degrees C gives k = 5.8 x 10(-10) s-1.M-1. The activation energy for the process was estimated to be 24 kcal/mole. In D2O solutions essential lowering of the activation energy (13 kcal/mole) and rising of rate constant (k = 3.7 x 10(-9) s-1.M-1 at 37 degrees C) were observed. The strong influence of D2O on the process points to the possible participation of singlet oxygen in a heat-induced formation of 8-oxy-dGMP. The obtained values of rate constants and activation energy induced by heat show that of all types of DNA damages currently known such as single strand scission, depurination, cytosine deamination and oxidation of guanyl residues to the 8-oxo-derivatives- the last process seems to be the strongest damage of DNA resulting in such biological consequences as mutagenesis, carcinogenesis and aging.
Mol Biol (Mosk)
PMID:[Kinetics of formation of 8-oxy-2'-deoxyguanosine-5'-monophosphate under the effect of heat: determination of rate constants and activation energy]. 133 39

Differential scanning microcalorimetry was used to study thermal stability of the ferro- and ferriforms of hemoglobin at pH 7.4 in phosphate buffer and in buffer mixtures of methanol, ethanol, 1-propanol. Denaturation of the human hemoglobin molecule composed of four subunits was cooperative transition. The thermostability of the hemoglobin forms decreased in the order of carboxyhemoglobin (TD = 82.0 degrees C) > oxyhemoglobin (71.0 degrees C) > methemoglobin (67.0 degrees C). The aliphatic alcohols as cosolvents decreased the hemoglobin stability because of loosening the structure of the globin moiety by disturbing its hydrophobic contacts and hydrogen bonds. These alcohols reduced the oxygen affinity for hemoglobin probably due to perturbation of the R<-->T equilibrium by the decreased bulk dielectric constant of the solvent. Oxyhemoglobin and methemoglobin was converted to hemichrome by high alcohol concentrations.
Mol Biol (Mosk)
PMID:[Thermal stability and functional properties of human hemoglobin in the presence of aliphatic alcohols]. 133 52

The processes of reversible oxygen binding and nonreversible autoxidation of human hemoglobin were studied. The activation energy of the oxygen binding, as determined by the temperature dependence of the P50 parameter, was 26 +/- 4 kJ/mol, the activation energy of the autoxidation, as determined by the temperature dependence of the apparent rate constant of autoxidation, was 120 +/- 15 kJ/mol. Pyridoxal phosphate decreased the oxygen affinity of hemoglobin, slightly diminished the cooperativity of the oxygenation process and unaffected the activation energy of the oxygen binding. Pyridoxal phosphate slightly reduced the Bohr coefficient value from 0.70 to 0.65. Pyridoxal phosphate, but not pyridoxal, raised the apparent rate constant of autoxidation reaction. The rate of autoxidation significantly increased as the pH value of the medium decreased, reflecting, probably, protonation of the distal histidine of the hemoglobin. The activation energy of autoxidation was independent of pH. Aliphatic alcohols also increased the rate of the autoxidation process, probably, either by stabilization of the hemoglobin T-state, or by direct nucleophilic displacement of the oxygen molecule.
Mol Biol (Mosk)
PMID:[Autooxidation and oxygenation of human hemoglobin]. 133 53


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