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H Sies

Publications and source records attributed to H Sies.

At least 55 records · Page 3Linked to original sources
PubMed2000

Water-soluble organotellurium compounds: catalytic protection against peroxynitrite and release of zinc from metallothionein.

The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc storage protein, metallothionein, by tert-butyl hydroperoxide is also catalyzed by the water-soluble organotellurium compounds. As compared to selenium-containing compounds (e.g., ebselen and selenocystamine), some of the tellurides that were tested ¿e.g., 3-[4-(N,N-dimethylamino)benzenetellurenyl]propanesulfonic acid, sodium salt¿ exhibit a significantly higher reactivity in these assays, making them some of the most effective compounds tested thus far. The catalysis of destruction of zinc-sulfur clusters by water-soluble organotellurium compounds could have implications for the bioavailability of zinc in vivo. These compounds might be lead compounds for the development of a new class of water-soluble, tellurium-based antioxidant and zinc-releasing drugs.

Benzoates↗
PubMed2000

One-electron reduction of selenomethionine oxide.

Experimental evidence is provided that selenomethionine oxide (MetSeO) is more readily reducible than its sulfur analogue, methionine sulfoxide (MetSO). Pulse radiolysis experiments reveal an efficient reaction of MetSeO with one-electron reductants, such as e(aq)-, (k = 1.2x10(10) M(-1) s(-1)), CO2*- (k = 5.9x10(8) M(-1) s(-1)) and (CH3)2 C*OH (k = 3.5x10(7) M(-1) s(-1)), forming an intermediate selenium-nitrogen coupled zwitterionic radical with the positive charge at an intramolecularly formed Se(three-electron bond)N 2sigma/1sigma* three-electron bond, which is characterized by an optical absorption with lambda(max) at 375 nm, and a half-life of about 70 micros. The same transient is generated upon HO* radical-induced one-electron oxidation of selenomethionine (MetSe). This radical thus constitutes the redox intermediate between the two oxidation states, MetSeO and MetSe. Time-resolved optical data further indicate sulfur-selenium interactions between the Se(three-electron bond)N transient and GSH. The Se(three-electron bond)N transient appears to play a key role in the reduction of selenomethionine oxide by glutathione.

Chemical Phenomena↗
PubMed2000

Carotenoid-containing unilamellar liposomes loaded with glutathione: a model to study hydrophobic-hydrophilic antioxidant interaction.

Unilamellar liposomes are used as a simple two-compartment model to study the interaction of antioxidants. The vesicle membrane can be loaded with lipophilic compounds such as carotenoids or tocopherols, and the aqueous core space with hydrophilic substances like glutathione (GSH) ascorbate, mimicking the interphase between an aqueous compartment of a cell and its surrounding membrane. Unilamellar liposomes were used to investigate the interaction of GSH with the carotenoids lutein, beta-carotene and lycopene in preventing lipid peroxidation. Lipid peroxidation was initiated with 2,2'-azobis-[2,4-dimethylvaleronitrile] (AMVN). Malondialdehyde (MDA) formation was measured as an indicator of oxidation; additionally, the loss of GSH was followed. In liposomes without added antioxidant, MDA levels of 119 +/- 6 nmol/mg phospholipid were detected after incubation with AMVN for 2 h at 37 degrees C. Considerably lower levels of 57 +/- 8 nmol MDA/mg phospholipid were found when the liposomal vesicles had been loaded with GSH. Upon incorporation of beta-carotene, lycopene or lutein, the resistance of unilamellar liposomes towards lipid peroxidation was further modified. An optimal further protection was observed with 0.02 nmol beta-carotene/mg phospholipid or 0.06 nmol lycopene/mg phospholipid. At higher levels both these carotenoids exhibited prooxidant effects. Lutein inhibited lipid peroxidation in a dose-dependent manner between 0.02 and 2.6 nmol/mg phospholipid. With increasing levels of lycopene and lutein the consumption of encapsulated GSH decreased moderately, and high levels of beta-carotene led to a more pronounced loss of GSH. The data demonstrate that interactions between GSH and carotenoids may improve resistance of biological membranes towards lipid peroxidation. Different carotenoids exhibit specific properties, and the level for optimal protection varies between the carotenoids.

Antioxidants↗
PubMed2000

Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans.

BACKGROUND: Carotenoids and tocopherols, known to be efficient antioxidants and capable of scavenging reactive oxygen species generated during photooxidative stress, may protect the skin from ultraviolet light-induced erythema. beta-Carotene is widely used as an oral sun protectant but studies on its protective effects are scarce. OBJECTIVE: The objective of this study was to investigate the protective effects of oral supplementation with carotenoids and a combination of carotenoids and vitamin E against the development of erythema in humans. DESIGN: A carotenoid supplement (25 mg total carotenoids/d) and a combination of the carotenoid supplement and vitamin E [335 mg (500 IU) RRR-alpha-tocopherol/d] were given for 12 wk to healthy volunteers. Erythema was induced by illumination with a blue-light solar simulator. Serum beta-carotene and alpha-tocopherol concentrations and skin carotenoid levels were assessed by HPLC and reflection photometry. RESULTS: Serum beta-carotene and alpha-tocopherol concentrations increased with supplementation. Erythema on dorsal skin (back) was significantly diminished (P < 0.01) after week 8, and erythema suppression was greater with the combination of carotenoids and vitamin E than with carotenoids alone. CONCLUSION: The antioxidants used in this study provided protection against erythema in humans and may be useful for diminishing sensitivity to ultraviolet light.

Adult↗
PubMed2000

Reactions of peroxynitrite with cocoa procyanidin oligomers.

Peroxynitrite is a mediator molecule in inflammation, and its biological properties are being studied extensively. Flavonoids, which are natural plant constituents, protect against peroxynitrite and thereby could play an anti-inflammatory role. Procyanidin oligomers of different sizes (monomer through nonamer), isolated from the seeds of Theobroma cacao, were recently examined for their ability to protect against peroxynitrite-dependent oxidation of dihydrorhodamine 123 and nitration of tyrosine and were found to be effective in attenuating these reactions. The tetramer was particularly efficient at protecting against oxidation and nitration reactions. Epicatechin oligomers found in cocoa powder and chocolate may be a potent dietary source for defense against peroxynitrite.

Biflavonoids↗
PubMed2000

Responses to peroxynitrite in yeast: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a sensitive intracellular target for nitration and enhancement of chaperone expression and ubiquitination.

Peroxynitrite (ONOO-), a potent oxidizing and nitrating species, has been linked to covalent modifications of biomolecules in a number of pathological conditions. In S. cerevisiae, a model eukaryotic cell system, ONOO- was found to be more potent than hydrogen peroxide in oxidizing thiols, inducing heat shock proteins (Hsp70) and enhancing the ubiquitination of proteins. As identified by microsequence analysis following immunoprecipitation with anti-nitrotyrosine antibodies, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was especially susceptible to nitration by ONOO- in yeast cells. The activity of this enzyme was strongly inhibited upon steady-state exposure of the cells to low doses of ONOO- in yeast and in cultured rat astrocytes. Thus, ONOO- is a potent stressor in yeast capable of inducing oxidative damage and protein nitration, with GAPDH being a preferential target protein that is efficiently inactivated.

Animals↗
PubMed2000

Binding of selenoprotein P to heparin: characterization with surface plasmon resonance.

The binding of selenoprotein P to glycosaminoglycans using heparin as a model compound was studied by surface plasmon resonance. It was found that heparin contains two binding sites for selenoprotein P, a high-affinity, low-capacity site (Kd approximately 1 nM) and a low-affinity, high-capacity site (Kd approximately 140 nM). Binding at both sites is sensitive to pH and ionic strength, and the high-affinity site is abolished by histidine carbethoxylation with diethylpyrocarbonate. The pH and salt dependence of binding suggests electrostatic interactions with heparin. The concentrations of selenoprotein P in plasma (approximately 50 nM) are sufficiently high to facilitate binding of selenoprotein P to proteoglycans on the vascular endothelium, and this may contribute to the formation of a protective barrier against oxidants such as peroxynitrite or hydroperoxides.

Heparin↗
PubMed2000

Ebselen: prospective therapy for cerebral ischaemia.

Stroke occurs due to haemorrhage or occlusive injury and results in ischaemia and reperfusion injury. A variety of destructive mechanisms are involved including oxygen radical generation, calcium overload, cytotoxicity and apoptosis as well as the generation of inflammatory mediators. Ebselen, 2-phenyl-1, 2-benzisoselenazol-3(2H)-one (PZ 51, DR3305), is a mimic of GSH peroxidase which also reacts with peroxynitrite and can inhibit enzymes such as lipoxygenases, NO synthases, NADPH oxidase, protein kinase C and H(+)/K(+)-ATPase. Ebselen is in a late stage of development for the treatment of stroke. The molecular actions of ebselen contribute to its anti-inflammatory and anti-oxidant properties, which have been demonstrated in a variety of in vivo models. Numerous in vitro experiments using isolated LDL, liposomes, microsomes, isolated cells and organs have established that ebselen protects against oxidative challenge. Unlike many inorganic and aliphatic selenium compounds, ebselen has low toxicity as metabolism of the compound does not liberate the selenium moiety, which remains within the ring structure. Subsequent metabolism involves methylation, glucuronidation and hydroxylation. Experimental studies in rats and dogs have revealed that ebselen is able to inhibit both vasospasm and tissue damage in stroke models, which correlates with its inhibitory effects on oxidative processes. Results from randomised, placebo-controlled, double-blind clinical studies on the neurological consequences of acute ischaemic stroke, subarachnoid haemorrhage and acute middle cerebral artery occlusion, have revealed that ebselen significantly enhances outcome in patients who have experienced occlusive cerebral ischaemia of limited duration. The benefit achieved with ebselen is closely related to the rapidity with which the treatment is initiated, following the onset of the stroke attack. Safety and tolerability are good and no adverse effects have become apparent. Ebselen is currently at the pre-registration stage for subarachnoid haemorrhage and stroke in Japan.

Animals↗
PubMed1999

Protection against peroxynitrite by cocoa polyphenol oligomers.

Flavonoids, natural plant constituents, protect against peroxynitrite and can thereby play a role in defense against this mediator of inflammation. Procyanidin oligomers of different size (monomer through nonamer), isolated from the seeds of Theobroma cacao, were examined for their ability to protect against peroxynitrite-dependent oxidation of dihydrorhodamine 123 and nitration of tyrosine. By molarity, oligomers were more effective than the monomeric epicatechin; the tetramer was particularly efficient at protecting against oxidation and nitration reactions. These results suggest that epicatechin oligomers found in cocoa powder and chocolate may be a potent dietary source for defense against peroxynitrite.

Biflavonoids↗
PubMed1999

Quantification of the alpha- and gamma-tocopherol metabolites 2,5,7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman and 2,7, 8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman in human serum.

alpha- and gamma-tocopherol are the major vitamin E compounds found in human blood and tissues. The metabolites are 2,5,7, 8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) and 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxychroman (gamma-CEHC, LLU-alpha), respectively. alpha-CEHC is excreted mainly as glucuronide or sulfate conjugates in the urine. Here we describe a sensitive and reliable method to analyze alpha- and gamma-CEHC in human serum. The concentration of alpha-CEHC in human serum is in the range of 5-10 pmol/ml but increases significantly up to 200 pmol/ml upon supplementation with RRR-alpha-tocopherol. About one-third of the alpha-CEHC circulating in the blood is present as a glucuronide conjugate. Baseline levels of gamma-CEHC are about 50 to 85 pmol/ml.

Adult↗
PubMed1999

Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion.

Mutations of mitochondrial (mt) DNA accumulate during normal aging. The most frequent mutation is a 4,977-base pair deletion also called the common deletion, which is increased in photoaged skin. Oxidative stress may play a major role in the generation of large scale mtDNA deletions, but direct proof for this has been elusive. We therefore assessed whether the common deletion can be generated in vitro through UV irradiation and whether reactive oxygen species are involved in this process. Normal human fibroblasts were repetitively exposed to sublethal doses of UVA radiation and assayed for the common deletion employing a semiquantitative polymerase chain reaction technique. There was a time/dose-dependent generation of the common deletion, attributable to the generation of singlet oxygen, since the common deletion was diminished when irradiating in the presence of singlet oxygen quenchers, but increased when enhancing singlet oxygen half-life by deuterium oxide. The induction of the common deletion by UVA irradiation was mimicked by treatment of unirradiated cells with singlet oxygen produced by the thermodecomposition of an endoperoxide. These studies provide evidence for the involvement of reactive oxygen species in the generation of aging-associated mtDNA lesions in human cells and indicate a previously unrecognized role of singlet oxygen in photoaging of human skin.

Cell Survival↗
PubMed1999

Biological activities of Apo-canthaxanthinoic acids related to gap junctional communication.

Apo-carotenoids with different numbers of conjugated double bonds are formed upon eccentric cleavage of carotenoids. These compounds may exhibit biological activities similar to those of the parent carotenoids or their central cleavage products, the retinoids. 11-Apo-canthaxanthin-11-oic acid, 13-apo-canthaxanthin-13-oic acid, and 14'-apo-canthaxanthin-14'-oic acid, carrying 2, 3, or 5 conjugated double bonds in the polyene chain, respectively, were tested for their effects on gap junctional communication (GJC), on stabilization of connexin43 mRNA, and on the activation of the retinoic acid-beta2 receptor (RAR-beta2 receptor); the effects were compared to those of retinoic acid and 4-oxo-retinoic acid, known to stimulate GJC and to activate the RAR-beta2 receptor. The effects of 4-oxo-retinoic acid were comparable to those of retinoic acid. 4-Oxo-retinoic acid, like retinoic acid, influences the stability of connexin 43 mRNA via elements located in the 3'-UTR. No effects were observed with the short-chain apo-canthaxanthinoic acids. A small but statistically significant induction of GJC and transactivation activity towards the RARbeta2 was found with 14'-apo-canthaxanthin-14'-oic acid. This might be due to biological effects of the compound itself or to biologically active breakdown products. The data suggest that the major biological effects of canthaxanthin on retinoid signaling pathways are related to activities mediated by the products of the central cleavage.

Canthaxanthin↗
PubMed1999

Activation pattern of mitogen-activated protein kinases elicited by peroxynitrite: attenuation by selenite supplementation.

Peroxynitrite is a mediator of toxicity in pathological processes in vivo and causes damage by oxidation and nitration reactions. Here, we report a differential induction of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells by peroxynitrite. For the exposure of cultured cells with peroxynitrite, we employed a newly developed infusion method. At 6.5 microM steady-state concentration, the activation of p38 MAPK was immediate, while JNK1/2 and ERK1/2 were activated 60 min and 15 min subsequent to 3 min of exposure to peroxynitrite, respectively. Protein-bound 3-nitrotyrosine was detected. When cells were grown in a medium supplemented with sodium selenite (1 microM) for 48 h, complete protection was afforded against the activation of p38 and against nitration of tyrosine residues. These data suggest a new role for peroxynitrite in activating signal transduction pathways capable of modulating gene expression. Further, the abolition of the effects of peroxynitrite by selenite supplementation suggests a protective role of selenium-containing proteins.

Animals↗
PubMed1999

Protection against peroxynitrite.

Peroxynitrite formed in vivo from superoxide and nitric oxide can mediate oxidation, nitration, or nitrosation reactions, leading to impaired function, toxicity, and alterations in signaling pathways. Protection against peroxynitrite is important for defense of normal tissue, especially during inflammation. Biological protection against peroxynitrite is organized in three categories: prevention, interception, and repair. Prevention is the control of the formation of peroxynitrite precursors, nitric oxide and superoxide. Interception is by direct reaction with peroxynitrite, leading to non-toxic products. In this regard, organoselenium compounds, metalloporphyrin derivatives, and peroxidases (e.g. glutathione peroxidase and myeloperoxidase) exhibit high second-order rate constants with peroxynitrite. Ebselen, like glutathione peroxidase, protects in a catalytic fashion utilizing glutathione as reductant in the peroxynitrite reductase reaction. Protection by metalloporphyrins can be maintained through glutathione or ascorbate. Repair processes remove damaged products and restitute intact biomolecules.

Animals↗
PubMed1999

S-nitrosylation and S-glutathiolation of protein sulfhydryls by S-nitroso glutathione.

The modification of reactive protein sulfhydryls by S-nitrosoglutathione and other NO donors has been studied by gel isoelectric focusing. S-nitrosylated, unmodified, and S-glutathiolated protein forms are differentiated by this method. With specific antibodies for the protein of interest, both S-nitrosylation and S-glutathiolation of the protein were analyzed in mixtures obtained as soluble tissue or cell extracts. The effect of S-nitrosoglutathione (GSNO) on purified phosphorylase b, on carbonic anhydrase III in an extract from rat liver, and on H-ras expressed in Escherichia coli was examined. When fresh GSNO reacted with pure phosphorylase b, only S-nitrosylated forms of the protein were observed. Likewise the NO donors, amyl nitrite, spermine NONOate, and diethylamine NONOate, all generated S-nitrosylated phosphorylase b. When crude mixtures of proteins from rat liver (containing carbonic anhydrase III) or from E. coli (containing an overexpressed form of H-ras) were exposed to fresh GSNO, both the S-nitrosylated and the S-glutathiolated forms of the proteins were observed. It is suggested that reactive intermediates from the breakdown of GSNO are responsible for the observed S-glutathiolation. These experiments show that both S-nitrosylated and S-glutathiolated forms of proteins may be generated by the addition of GSNO to mixtures containing proteins with reactive sulfhydryls. These protein modifications may exhibit metabolic consequences independent of the release of nitric oxide.

Animals↗
PubMed1999

Glutathione and its role in cellular functions.

Glutathione (GSH) is the major cellular thiol participating in cellular redox reactions and thioether formation. This article serves as introduction to the FRBM Forum on glutathione and emphasizes cellular functions: What is GSH? Where does it come from? Where does it go? What does it do? What is new and noteworthy? Research tools, historical remarks, and links to current trends.

Animals↗