Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Unithiol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1996

Sodium 2,3-dimercapto-1-propanesulfonate (DMPS) treatment does not redistribute lead or mercury to the brain of rat.

Since there has been concern about whether any of the chelating agents used therapeutically might cause an initial redistribution of heavy metals to the brain and since the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (Dimaval, DMPS) has been used to treat heavy metal intoxication in humans, the hypothesis that DMPS does not redistribute and increase lead or mercuric ions in the brains of rats was tested. Lead acetate at a concentration of 50 mg/l was made available in the drinking water of rats for 86 days. Other rats received intraperitoneal injections of 0.50 mg Hg/kg (as mercuric chloride) each day for 5 days a week for a total of 32 or 41 days. Animals were divided into groups and given, i.p., either 0.27 mmol DMPS/kg body weight or saline, each day for 1, 2, 3 or 4 days. Lead or mercury concentrations of the brain were determined after each group received DMPS for the different number of days. DMPS treatment did not result in any initial increase of lead or mercuric ions in the brain. The mercury content of the kidney decreased. The results of these experiments demonstrated that lead or mercuric ions were not redistributed to or increased in the brains of rats during the initial days of DMPS treatment.

Administration, Oral↗
PubMed1996

The use of 212Pb-labeled monoclonal antibody in the treatment of murine erythroleukemia.

PURPOSE: The goals of this study were to learn whether the DOTA chelator was useful for targeting lead radionuclides (203,212 Pb) to cells and tissues invaded by the Rauscher leukemia virus (RVB3) and to investigate the therapeutic efficacy of targeted 212Pb in treating the murine leukemia. METHODS AND MATERIALS: Five to 6-week-old BALB/c mice were inoculated i.v. with RVB3. This virus causes marked splenomegaly and death by day 13 and day 70 postinfection, respectively. Biodistribution, tumor targeting, and toxicity studies were performed using varying doses of 212Pb-DOTA-103A. A heavy metal chelator, DMPS, was administered orally and parenterally in two phases of the toxicity study. RESULTS: Biodistribution studies showed marked tumor targeting (58% ID/g spleen) in mice treated with 203Pb-103A as compared with mice treated with control antibody B3 (4.6% ID/g spleen). Histologic cure was achieved in all leukemic mice treated with 20 muCi212Pb-103A; however, all of the mice died with leukopenia and secondary++ bacterial infections due to severe bone marrow toxicity. Nonleukemic mice and mice treated with 20 muCi212Pb-B3 experienced less marrow toxicity and longer survival. Coadministration of the heavy metal chelator did not diminish the bone marrow toxicity. CONCLUSION: An effective, nonlethal dose could not be established to treat this tumor. The severe bone marrow toxicity associated with this radionuclide may limit its usefulness in systemic radioimmunotherapy.

Animals↗
PubMed1980

Distribution and excretion of 203Hg2+ in rats after unitiol, spironolactone and polythiol resin treatment.

Rats were given 203HgCl2 i.v. at a dose level of 120 microgram of Hg2+ per rat. The effect of unitiol (UNI; sodium 2, 3-dimercaptopropanosulphonate) and a combined UNI, spironolactone (SPL) and polythiol resin treatment on wholebody retention, organ distribution and excretion were studied for 48 h. In both treated groups significant increases in excretion and decreases in whole-body retention of 203Hg were observed. In the combination-treated group significantly lower values of 203Hg in plasma, kidney and brain were found.

Animals↗
PubMed1996

Evaluation of dithiol chelating agents as potential adjuvants for anti-IL-2 receptor lead or bismuth alpha radioimmunotherapy.

The dithiol chelating agents 2,3-dimercapto-1-propanesulfonic acid (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were evaluated for use as potential adjuvants to reduce or prevent radiotoxicity in anti-interleukin-2 receptor (IL-2R) Lead-212 or Bismuth-212 alpha-radioimmunotherapy. DMPS was less toxic than DMSA to tumor cell lines in culture. No adverse effects on the ability of an anti-IL-2R monoclonal antibody (MAb) to bind to its specific antigen were detected using DMPS or DMSA at concentrations up to 600 ug/mL in 10% or 100% mouse serum. After a 5-day oral administration of chelating agent, neither acute nor chronic toxicities on blood hematology, blood chemistry or organ weights were observed for treated mice. DMPS and DMSA were effective in accelerating whole body clearance of the gamma-emitting tracer Bismuth-206. Both chelates significantly reduced femur uptake of tracer when compared to nontreated control mice. However, only DMPS prevented early (2 h postinjection) renal accumulation. These studies support the use of DMPS as a potential adjuvant chelation therapy in Lead-212 or Bismuth-212 radioimmunotherapy protocols.

Adjuvants, Immunologic↗
PubMed2006

Cadmium inhibits delta-aminolevulinate dehydratase from rat lung in vitro: interaction with chelating and antioxidant agents.

The effect of cadmium (Cd(2+)) on delta-aminolevulinate dehydratase (delta-ALA-D) activity from rat lung in vitro was investigated. delta-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd(2+) in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)(2), and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelatingxantioxidant agent) was also studied. Zinc chloride (ZnCl(2)) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on delta-ALA-D activity. Cadmium inhibited rat lung delta-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl(2) (100microM), protected the inhibition of enzyme activity caused by Cd(2+). Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl(2) restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of delta-ALA-D inhibition induced by Cd(2+). ZnCl(2) did not restore inhibition of enzyme activity caused by Cd(2+) plus chelating agents. Conversely, DTT restored the inhibition induced by Cd(2+)/DMSA, but not by Cd(2+)/DMPS. Antioxidants were not effective in ameliorating delta-ALA-D inhibition induced by Cd(2+), whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd(2+)xDMPSx(PhSe)(2) and Cd(2+)xDMPSxNAC was observed. There was no combined effect of Cd(2+)xchelatorxantioxidants when DMSA was used. This study demonstrated that Cd(2+)inhibited delta-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd(2+) in rat lung.

Acetylcysteine↗
PubMed2005

Intracellular redistribution of heme in rat liver under oxidative stress: the role of heme synthesis.

Heme distribution in subcellular fractions of rat liver was studied first hours under the action of several agents causing oxidative stress in vivo. Total and post-mitochondrial heme content in liver was found to depend on both the level of hemolysis products in blood and agent's capacity to modify heme and hemoproteins. The increase of activity of 5-aminolevulinate synthase (ALAS) and/or heme accumulation in mitochondria was accompanied by increase of tryptophan-2,3-dioxygenase (TDO) heme saturation. Membrane stabilisation by tocopherol or prevention of early ALAS induction by cycloheximide prevented both mitochondrial heme accumulation and increase of TDO heme saturation. Modification of heme fully prevented the alterations of total heme content even under severe hemolysis as well as the increase of TDO heme saturation if no increase of heme synthesis occurred. Thus heme synthesis can greatly contribute to heme intracellular redistribution under oxidative stress.

5-Aminolevulinate Synthetase↗
PubMed2004

Insights on the interaction of met-enkephalin with negatively charged membranes--an infrared and solid-state NMR spectroscopic study.

Enkephalins are pentapeptides found in the human nervous system, where they are involved in the relief of pain. The interaction of these neuropeptides with the nerve cell membranes would be a key-step in the receptor binding. We have used both Fourier-transform infrared and solid-state NMR spectroscopies to shed light on the interactions responsible for the association of enkephalins with negatively charged membranes. More specifically, we have investigated the interaction of methionine-enkephalin (Menk) with DMPG and DMPS vesicles. Our results suggest that Menk interacts electrostatically with both model membranes via its terminal NH3+ group. However, the peptide induced the formation of elongated DMPG vesicles in the magnetic field. On the other hand, the association of Menk with DMPS bilayers was concentration-dependent and disrupted the membrane at high peptide concentrations. The different effect of methionine-enkephalin with the two types of anionic membranes is most likely related to the different fluidity of these systems.

Anions↗
PubMed2006

GEA3162, a nitric oxide-releasing agent, activates non-store-operated Ca2+ entry and inhibits store-operated Ca2+ entry pathways in neutrophils through thiol oxidation.

We demonstrated that 5-amino-3-(3,4-dichlorophenyl)1,2,3,4-oxatriazolium (GEA3162), a nitric oxide (NO)-releasing agent, stimulated [Ca2+]i rise in rat neutrophils. This Ca2+ response was prevented by the thiol reducing agents, 2-mercaptoethanol, N-acetyl-L-cysteine, dithiothreitol, 2,3-dimercaptopropane-1-sulfonic acid (DMPS) and tris-(2-carboxyethyl)phosphine (TCEP), but slightly reduced by the antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). GEA3162 also increased the formation of cellular reactive oxygen intermediates and decreased the cellular content of low molecular thiols. These responses were greatly reduced by Trolox, dithiothreitol and N-acetyl-L-cysteine. GEA3162 stimulated the protein tyrosine phosphorylation in neutrophils. The [Ca2+]i rise caused by formyl-Met-Leu-Phe (fMLP) and cyclopiazonic acid (CPA) was suppressed by GEA3162. TCEP prevented the inhibition of fMLP-induced [Ca2+]i rise by GEA3162. In the absence of external Ca2+, GEA3162 inhibited the CPA-induced [Ca2+]i rise, whereas it only slightly affected the fMLP-induced mobilization of the Ca2+ store. Application of GEA3162 after the stimulation with fMLP or CPA suppressed the robust Ca2+ entry followed by the readdition of Ca2+ into medium. Moreover, the Ca2+ entry was more susceptible to inhibition by treatment with GEA3162 prior to than after the fMLP stimulation. GEA3162 had no effect on the mitochondrial membrane potential. GEA3162 induced actin reorganization and condensed filament network at the cell periphery. These results indicate that GEA3162 exerted both the stimulation of Ca2+ entry and the inhibition of the store-operated Ca2+ entry in rat neutrophils. The dual effects of GEA3162 on the regulation of the external Ca2+ entry are mainly through the thiol modification of target protein(s) residing on the outside of the plasma membrane.

Acetylcysteine↗
PubMed2005

Efficacy of 2,3-dimercapto-1-propanesulfonic acid (DMPS) and diphenyl diselenide on cadmium induced testicular damage in mice.

The deleterious effect of acute cadmium-intoxication in mice testes was evaluated. Animals received a single dose of CdCl2 (2.5 or 5 mg/kg, intraperitoneally) and a number of toxicological parameters in mice testes were examined, such as delta-aminolevulinic acid dehydratase (delta-ALA-D) activity, lipid peroxidation, hemoglobin and ascorbic acid contents. Furthermore, the parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were also determined. Thus, a possible protective effect of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) and diphenyl diselenide (PhSe)2 were studied. The results demonstrated an inhibition of delta-ALA-D activity, a reduction of ascorbic acid and an increase of lipid peroxidation induced by cadmium, indicating testes damage. Furthermore, we observed an increase of plasma LDH, AST and ALT activities. DMPS (400 mol/kg) and (PhSe)2 (100 micromol/kg) partially protected from the inhibitory effect of 2.5 mg/kg CdCl2 on delta-ALA-D and from the increase of TBARS (thiobarbituric acid reactive species) levels. (PhSe)2 therapy was effective in ameliorate ascorbic acid content when the cadmium dose was 2.5 mg/kg. Treatment with DMPS and (PhSe)2, individually or combined, was inefficient in reducing cadmium-induced plasma LDH and ALT activity increase. The use of combined therapy (DMPS plus (PhSe)2) proved to be efficient in decreasing cadmium levels in testes and in ameliorating plasma AST activity from animals that received the highest dose of cadmium.

Alanine Transaminase↗
PubMed2005

Effect of the polar headgroup of phospholipids on their interaction with actin.

It is generally admitted that actin filaments are anchored to a membrane by membranar actin-binding-proteins. However, we found that actin may also interact directly with membrane phospholipids. The actin-phospholipid complex has been investigated at the air-water interface using a film balance technique. In order to probe the effect of the phospholipid headgroup on the actin-phospholipid interaction, we focus mainly on phospholipids that have the same acyl chain length but different headgroups. For all the phospholipids, the apparent area per molecule (the total surface divided by the number of lipid molecules) increases after the injection of the protein into the subphase, which suggests an intercalation of actin between the phospholipid molecules. This effect seems to be more important for DMPE and DMPS than for DMPG, suggesting that the headgroup plays an important role in this intercalation. The critical surface pressure associated to the liquid expanded-liquid condensed (LE-LC) phospholipid transition increases with the concentration of G-actin and thus suggests that G-actin acts as an impurity, simply competing as a surfactant at the air-water interface. On the other hand, F-actin affects the LE to LC transition of phospholipids differently. In this case, the LE to LC transition is broader and F-actin slightly decreases the critical surface pressure, which suggests that electrostatic interactions are involved.

Actin Cytoskeleton↗
PubMed2005

Arsenic induced blood and brain oxidative stress and its response to some thiol chelators in rats.

Chronic arsenic toxicity is a widespread problem, not only in India and Bangladesh but also in various other regions of the world. Exposure to arsenic may occur from natural or industrial sources. The treatment that is in use at present employs administration of thiol chelators, such as meso 2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), which facilitate its excretion from the body. However, these chelating agents are compromised with number of limitations due to their lipophobic nature, particularly for their use in cases of chronic poisoning. During chronic exposure, arsenic gains access into the cell and it becomes mandatory for a drug to cross cell membrane to chelate intracellular arsenic. To address this problem, analogs of DMSA having lipophilic character, were examined against chronic arsenic poisoning in experimental animals. In the present study, therapeutic efficacy of meso 2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), monoisoamyl DMSA (MiADMSA) were compared in terms of reducing arsenic burden, as well as recovery in the altered biochemical variables particularly suggestive of oxidative stress. Adult male Wistar rats were given 100-ppm arsenic for 10 weeks followed by chelation therapy with the above chelating agents at a dose of 50 mg/Kg (orally) once daily for 5 consecutive days. Arsenic exposure resulted in marked elevation in reactive oxygen species (ROS) in blood, inhibition of ALAD activity and depletion of GSH. These changes were accompanied by significant decline in blood hemoglobin level. MiADMSA was the most effective chelator in reducing ROS in red blood cells, and in restoring blood ALAD compared to two other chelators. Brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) decreased, while ROS and TBARS increased significantly following arsenic exposure. There was a significant increase in the activity of glutathione-S-transferase (GST) with a corresponding decline in its substrate i.e. glutathione. Among all the three chelators, MiADMSA showed maximum reduction in the level of ROS in brain. Additionally, administration of MiADMSA was most effective in counteracting arsenic induced inhibition in brain ALAD, SOD and GPx activity. Based on these results and in particular higher metal decorporation from blood and brain, we suggest MiADMSA to be a potential drug of choice for the treatment of chronic arsenic poisoning. However, further studies are required for the choice of appropriate dose, duration of treatment and possible effects on other major organs.

5-Aminolevulinate Synthetase↗
PubMed2005

2,3-Dimercaptopropanol, 2,3-dimercaptopropane-1-sulfonic acid and meso-2,3-dimercaptosuccinic acid increase lead-induced inhibition of delta-aminolevulinate dehydratase in vitro and ex vivo.

We investigated the effects of dimercaprol (BAL), meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-1-propanesulphonic acid (DMPS) on human blood delta-aminolevulinate dehydratase (delta-ALA-D) activity, the most reliable indicator of lead intoxication in humans, in the presence of lead in vitro. Furthermore, we studied the effects of the chelating agents, administered subcutaneously, on delta-ALA-D activity in blood and tissues of mice submitted to sub-acute lead exposure (50 mg/kg for 15 consecutive days, subcutaneously). In vitro results demonstrated that human blood delta-ALA-D activity was significantly inhibited (62%) by lead acetate. Lead acetate (1-1000 microM) pre-incubated with human blood increased the inhibitory potency of this compound on delta-ALA-D when compared to the assay without pre-incubation (89%). Chelating agents caused a marked potentiation of delta-ALA-D inhibition induced by lead, in vitro. One of the most notable observations in the present study was the correspondence between in vitro and ex vivo effects. In fact, BAL and DMPS increase the inhibitory effect of lead on delta-ALA-D activity from mice blood. The complexes formed (lead and chelators) were more inhibitory than lead alone in kidney and liver enzyme activity, ex vivo.

Animals↗
PubMed2005

Simultaneous administration of sodium selenite and mercuric chloride decreases efficacy of DMSA and DMPS in mercury elimination in rats.

Two chelating agents meso-2,3-dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercapto-propane-1-sulphonate (DMPS) were tested for their efficiency in mercury removal from the body of rats in the presence and in the absence of selenium. Female Wistar rats were given a single intraperitoneal injection of mercuric chloride or an equimolar mixture of mercuric chloride and sodium selenite (1.5 micromol/kg body weight). The chelating agents were given orally, in excess (500 micromol DMSA/kg body weight; 300 micromol DMPS/kg body weight), 30 min after the administration of mercury and selenium. The animals were euthanized 24 h after the treatment and mercury in the kidney, liver, and 24 h urine was determined using cold vapour atomic absorption spectrometry (CV-AAS). The simultaneous administration of mercuric chloride and sodium selenite led to a redistribution of mercury in the organs, so that accumulation of mercury in the kidneys was decreased and in the liver increased. Selenite also caused decrease in the level of urinary mercury excretion. Both chelating agents were effective in mercury removal from the body, by increasing its urinary excretion. However, when animals were simultaneously treated with mercury and selenite, the rise of mercury excreted in the urine due to the treatment with chelating agents was lower when compared to animals receiving mercury without selenite. It is concluded that sodium selenite decreases the efficiency of DMSA and DMPS in mercury removal from the body of rats.

Animals↗
PubMed2001

The interaction of trichosanthin with supported phospholipid membranes studied by surface plasmon resonance.

Trichosanthin (TCS) is a toxic protein isolated from a Chinese herbal medicine, the root tuber of Trichosanthes kirilowii Maximowicz of the Curcurbitaceae family. It is now used in China to terminate early and mid-trimester pregnancies. The ribosome inactivating property is thought to be account for its toxicity; it can inactivate the eukaryotic ribosome through its RNA N-glycosidase activity. The interactions of TCS with biological membrane is thought to be essential for its physiological effect, for it must get across the membrane before it can enter the cytoplasm and exert its RIP function. In the present work, the interaction of TCS with supported phospholipid monolayers is studied by surface plasmon resonance. The results show that electrostatic forces dominate the interaction between TCS and negatively charged phospholipid containing membranes under acid condition and that both the pH value and the ionic strength can influence its binding. It is proposed that, besides electrostatic forces, hydrophobic interaction may also be involved in the binding process.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Attenuated total reflection (ATR) Fourier transform infrared spectroscopy of dimyristoyl phosphatidylserine-cholesterol mixtures.

Mixtures of cholesterol with dimyristoyl phosphatidylserine or deuterated dimyristoyl phosphatidylserine were investigated by polarized and non polarized attenuated total reflection (ATR) Fourier transform infrared (FTIR) Spectroscopy. From polarized spectra the dichroic ratios of various vibrations as a function of cholesterol were calculated. Dichroic ratios of methylene vibration (CH(2)) 2934 cm(-1) of cholesterol decreases with increase of cholesterol concentration leveling off in the region where cholesterol phase separation takes place. The orientation of deuterated methylene (CD(2)) symmetric and asymmetric bands of the deuterated dimyristoyl phosphatidylserine is influenced little by cholesterol. In the polar region of dimyristoyl phosphatidylserine no effect of cholesterol on the dichroic ratios of carbonyl (C==O) and asymmetric phosphate (PO(2)(-)) vibrations were detected. For nonpolarized spectra the broad bands in the polar region of the phospholipid were deconvoluted. The carbonyl band (C==O) in pure dimyristoyl phosphatidylserine is composed of five bands; in the presence of increasing concentrations of cholesterol conformational change of these vibrations takes place evolving into one predominant band. Similar conformational change takes place in the presence of 75 molecules water/molecule DMPS. For the asymmetric phosphate band very small shifts due to interaction with cholesterol were detected.

Cholesterol↗
PubMed2002

Transdermal insulin delivery using lipid enhanced electroporation.

Transdermal insulin transport by electroporation was measured using porcine epidermis and fluorescein-labeled insulin. Previous studies have shown that anionic lipids can enhance the electroporative transport of molecules up to 10 kDa in size. It was also shown that it is the charge and not the type of the phospholipid head group that influences transdermal transport under electroporation. Moreover, phospholipids with saturated acyl chains enhance the transport of larger molecules more as compared to those with unsaturated chains. In the current study, based on those earlier findings, the effect of 1,2-dimyristoyl-3-phosphatidylserine (DMPS) on the transdermal transport of insulin by electroporation was examined. Porcine epidermis was used as a model for skin. Transport was measured using glass vertical diffusion apparatus in which the epidermis separated the donor and receiver compartments. Negative pulses were applied across the epidermis using platinum electrodes. Results show that when electroporation was carried out in the presence of DMPS, there was greater than 20-fold enhancement of insulin transport. Furthermore, while in the presence of the phospholipid, almost all the transported insulin was detected in the receiver compartment; in the absence of added lipids, only about half the insulin transported was in the receiver compartment and an almost equal amount of insulin remained in the epidermis. Fluorescence microscopy revealed that the insulin transport was mainly through the lipid multilayer regions that surround the corneocytes.

Administration, Cutaneous↗
PubMed2000

Selective destabilization of acidic phospholipid bilayers performed by the hepatitis B virus fusion peptide.

A peptide corresponding to the N-terminal region of the S protein of hepatitis B virus (Met-Glu-Asn-Ile-Thr-Ser-Gly-Phe-Leu-Gly-Pro-Leu-Leu-Val-Leu-Gln) has been previously demonstrated to perform aggregation and destabilization of acidic liposome bilayers and to adopt a highly stable beta-sheet conformation in the presence of phospholipids. The changes in the lipid moiety produced by this peptide have been followed by fluorescence depolarization and electron microscopy. The later was employed to determine the size and shape of the peptide-vesicle complexes, showing the presence of highly aggregated and fused structures only when negatively charged liposomes were employed. 1,6-Diphenyl-1,3,5-hexatriene depolarization measurements showed that the interaction of the peptide with both negatively charged and zwitterionic liposomes was accompanied by a substantial reduction of the transition amplitude without affecting the temperature of the gel-to-liquid crystalline phase transition. These data are indicative of the peptide insertion inside the bilayer of both types of liposomes affecting the acyl chain order, though only the interaction with acidic phospholipids leads to aggregation and fusion. This preferential destabilization of the peptide towards negatively charged phospholipids can be ascribed to the electrostatic interactions between the peptide and the polar head groups, as monitored by 1-(4-(trimethylammoniumphenyl)-6-phenyl-1,3, 5-hexatriene fluorescence depolarization analysis.

Amino Acid Sequence↗
PubMed1997

Binding of mercury in renal brush-border and basolateral membrane-vesicles.

The influence of the thiols L-cysteine (CYS), glutathione (GSH), and 2,3-dimercapto-1-propanesulfonate (DMPS) on the binding and transport of inorganic mercury (Hg2+) in luminal (brush-border) and basolateral membrane-vesicles isolated from the kidneys of rats was studied using radiolabeled mercury (203HgCl2). Membrane-vesicles were exposed to 1, 10, or 100 microM Hg2+ in the presence or absence of a 3:1 or 10:1 mole-ratio of CYS, GSH, or DMPS relative to Hg2+. Equilibration of mercury with the membrane-vesicles occurred very rapidly, essentially being complete within 5 sec. By 60 sec, binding accounted for 87-97% of intravesicular Hg2+ in the absence of exogenous thiols. All three thiols significantly reduced the fraction of binding, with DMPS being the most effective agent. CYS enhanced the association of Hg2+ with luminal membrane-vesicles relative to that when Hg2+ was added alone, suggesting that conjugation of Hg2+ with CYS promotes the transport of low concentrations of Hg2+. In contrast, an excess of either GSH or DMPS relative to Hg2+ interfered significantly with both the binding and transport of Hg2+ into either luminal or basolateral membrane-vesicles. In summary, the present study is the first to describe the association of Hg2+ with renal luminal and basolateral membrane-vesicles. Evidence was obtained for the involvement of a Hg2+-CYS conjugate as a mechanism by which Hg2+ uptake and binding to luminal membranes occur and for an inhibitory effect of GSH and the chelator DMPS with regard to Hg2+ uptake and binding, demonstrating that extracellular thiols can modulate significantly the renal accumulation of Hg2+.

Animals↗