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Query: UNIPROT:P06889 (Mol)
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Naphthalene is a bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Little information is available regarding the mechanism of naphthalene toxicity. We have assessed the oral, low dose (0.05 LD50) chronic effects of naphthalene (110 mg/kg/day p.o. in corn oil) for 120 consecutive days on lipid peroxidation and DNA fragmentation in the liver and brain tissues of female Sprague-Dawley rats. The animals were sacrificed on 0, 15, 30, 45, 60, 75, 90, 105 and 120 days of treatment. Maximum increases in hepatic and brain lipid peroxidation and DNA fragmentation were observed between 90 and 105 days of treatment. Following administration of naphthalene for 90 days, approximately 1.4- and 1.3-fold increases in lipid peroxidation were observed in the hepatic and brain tissues, respectively, while under the same conditions and time points 1.9- and 2.5-fold increases in hepatic and brain DNA fragmentation were observed, respectively. These results demonstrate that low dose chronic administration of naphthalene induces an oxidative stress resulting in tissue damaging effects that may contribute to the toxicity and carcinogenicity of naphthalene.
Res Commun Mol Pathol Pharmacol 1998 Sep
PMID:Induction of oxidative stress and DNA damage by chronic administration of naphthalene to rats. 987 83

The folding and assembly of the Fv fragment of the phosphorylcholine binding antibody McPC603, a non-covalent heterodimer of the variable domains VH and VL, was investigated. Since both domains, each engineered for stability and folding efficiency, could now be obtained in native and soluble form by themselves, fluorescence spectra of VH and VL in unfolded, folded and associated states can be reported. VH and VL only associate when they are native, and the stability of the heterodimer is strongly increased in the presence of antigen. VH rapidly folds into an hyperfluorescent intermediate, and the native state is reached in two parallel, proline-independent reactions. VL displays two fast refolding reactions, which are followed by two slower phases, limited by proline cis/trans-isomerization. The rate-limiting step for both the Fv and the scFv (single-chain Fv) fragment is the formation of the native VH-VL interface, which depends on ProL95 being in cis. The folding of the Fv fragment is fast after short-term denaturation or in the presence of proline cis/trans-isomerase catalysis, but the scFv fragment falls into a kinetic trap, observed by the persistence of the slow phases under all conditions. Furthermore, the scFv fragment, but not the Fv fragment, gives rise to premature interface formation, indicated by the fluorescence spectra and a much higher transient binding of 8-anilino-1-naphthalene sulfonate. The analysis of the folding pathway of the domains VH and VL in isolation and in non-covalent and covalent assemblies should provide helpful insights into the folding of multimeric proteins in general, and for the further engineering of stable and well-folding antibody fragments in particular.
J Mol Biol 1999 Feb 05
PMID:Folding and assembly of an antibody Fv fragment, a heterodimer stabilized by antigen. 992 81

The hydration of intestinal fatty acid binding protein (IFABP) in apo-form and complexed with palmitate, oleate, and 1-anilino-8-naphthalene sulfonate (ANS) has been studied by water 17O and 2H magnetic relaxation dispersion (MRD) measurements. These ligands bind in a large internal cavity, displacing most of the crystallographically identified cavity water molecules. Unlike most other proteins, IFABP gives rise to MRD profiles with two dispersion steps. The low-frequency dispersion yields a correlation time of 7 ns at 300 K, matching the known tumbling time of IFABP. The dispersion amplitude requires only three (apo) or four (holo) long-lived and ordered water molecules (residence time 0.01-4 microseconds at 300 K). Comparison of MRD profiles from the different complexes indicates that the displaced cavity water molecules are short-lived. The few long-lived (>10 ns) water molecules required by the MRD data are tentatively assigned to crystallographic hydration sites on the basis of accessibility, positional order, and H-bonding. The amplitude of the high-frequency dispersion corresponds to 10-20 moderately ordered water molecules, with a correlation time of ca. 1 ns that may reflect a transient opening of the cavity required for exchange with external water.
J Mol Biol 1999 Feb 12
PMID:Water molecules in the binding cavity of intestinal fatty acid binding protein: dynamic characterization by water 17O and 2H magnetic relaxation dispersion. 993 Dec 62

Recently, the novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) has been shown to inhibit cell growth and induce apoptosis in several human carcinoma cell lines. To understand the mechanism of AHPN action, we identified, using the differential display method, several genes that are differentially regulated by AHPN. The sequence of one of these genes was highly homologous to mouse MyD118, a gene closely related to GADD45. Both of these genes have been reported to play a role in negative growth control and apoptosis. hMyD118 was expressed in a variety of tissues, including liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, and peripheral blood leukocytes. The levels of both hMyD118 and GADD45 mRNA was rapidly increased in a number of carcinoma cell lines after treatment with AHPN. This increase was specific for AHPN because retinoic acid, a retinoic acid receptor-selective retinoid, and an retinoid X receptor-selective retinoid were ineffective. These results suggest that this action of AHPN involves a novel mechanism that is independent of the nuclear retinoid receptors. AHPN increases the half-life of hMyD118 and GADD45 mRNA by >9-fold, indicating that it causes an increase in the stability of these mRNAs. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoro-methylketone (ZVAD. fmk) had no effect on the induction of hMyD118, indicating that this increase occurred independently of caspase activation. Our study demonstrates that the inhibition of cell growth by AHPN is accompanied by an increase in hMyD118 and GADD45 mRNA, and that this enhancement is regulated at a post-transcriptional level. Our results support a role for MyD118 and GADD45 in the negative growth control by AHPN.
Mol Pharmacol 1999 Apr
PMID:Post-transcriptional regulation of MyD118 and GADD45 in human lung carcinoma cells during 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2- naphthalene carboxylic acid-induced apoptosis. 1010 Oct 24

The rotational spectra of cis- and trans-1-hydroxynaphthalene and trans-1-DO-naphthalene have been recorded between 6 and 18 GHz using a pulsed microwave spectrometer. Most of the transitions detected are a type; hyperfine splittings from the electric quadrupole interaction were observed for some transitions of the deuterated isotopomer. The frequencies were well modeled with an S-reduced asymmetric rotor Hamiltonian. The rotational constants were determined much more accurately than previously. In addition, the quartic centrifugal distortion parameters were determined for the first time. Their values were very small, consistent with the rigid framework of this aromatic molecule. Theoretical calculations were carried out to support the assignment of the two forms to the cis and trans conformers. These calculations suggested that the cis conformer is slightly nonplanar in its equilibrium configuration, a property which is not inconsistent with its rotational constants. Copyright 1999 Academic Press.
J Mol Spectrosc 1999 May
PMID:Rotational Spectra of Conformers and Isotopomers of 1-Hydroxynaphthalene. 1019 Nov 62

The dimeric protein, trp apo-repressor of Escherichia coli has been subjected to high hydrostatic pressure under a variety of conditions, and the effects have been monitored by fluorescence spectroscopic and infra-red absorption techniques. Under conditions of micromolar protein concentration and low, non-denaturing concentrations of guanidinium hydrochloride (GuHCl), tryptophan and 8-anilino-1-naphthalene sulfonate (ANS) fluorescence detected high pressure profiles demonstrate that pressures below 3 kbar result in dissociation of the dimer to a monomeric species that presents no hydrophobic binding sites for ANS. The FTIR-detected high pressure profile obtained under significantly different solution conditions (30 mM trp repressor in absence of denaturant) exhibits a much smaller pressure dependence than the fluorescence detected profiles. The pressure-denatured form obtained under the FTIR conditions retains about 50 % alpha-helical structure. From this we conclude that the secondary structure present in the high pressure state achieved under the conditions of the fluorescence experiments is at least as disrupted as that achieved under FTIR conditions. Fluorescence-detected pressure-jump relaxation studies in the presence of non-denaturing concentrations of GuHCl reveal a positive activation volume for the association/folding reaction and a negative activation volume for dissociation/unfolding reaction, implicating dehydration as the rate-limiting step for association/folding and hydration as the rate-limiting step for unfolding. The GuHCl concentration dependence of the kinetic parameters place the transition state at least half-way along the reaction coordinate between the unfolded and folded states. The temperature dependence of the pressure-jump fluorescence-detected dissociation/unfolding reaction in the presence of non-denaturing GuHCl suggests that the curvature in the temperature dependence of the stability arises from non-Arrhenius behavior of the folding rate constant, consistent with a large decrease in heat capacity upon formation of the transition state from the unfolded state. The decrease in the equilibrium volume change for folding with increasing temperature (due to differences in thermal expansivity of the folded and unfolded states) arises from a decrease in the absolute value for the activation volume for unfolding, thus indicating that the thermal expansivity of the transition state is similar to that of the unfolded state.
J Mol Biol 1999 May 07
PMID:Pressure-jump studies of the folding/unfolding of trp repressor. 1032 54

Naphthalene causes severe dose- and site-selective injury to mouse nonciliated bronchiolar (Clara) epithelial cells. Toxicity is characterized by exfoliation of injured Clara cells into the airway lumen 24 h after exposure. The purpose of this study was to define the temporal pattern of intracellular changes immediately following naphthalene treatment, with the goal of identifying critical early events involved in cytotoxicity. Mice were injected with naphthalene or carrier and were killed 1, 2, 3, and 6 h after treatment (PT). Loss of membrane integrity was assessed by ethidium homodimer-1 permeability and confocal microscopy. Cell morphology and ultrastructure were evaluated using high-resolution light and electron microscopy. Permeable cells were found only in terminal bronchioles and increased in abundance with time PT. At 2 and 3 h PT, when most Clara cells had early signs of injury, few permeable cells were detected. Many Clara cells had apical membrane blebs that contained abundant, swollen, smooth endoplasmic reticulum (SER) and few other organelles. By 6 h PT many Clara cells were membrane-permeable. However, many permeable Clara cells lacked apical blebs and SER was less abundant in these cells. Cytoplasmic blebbing may be a mechanism to protect the cell by isolating and removing damaged SER. We conclude that the early stages of injury include SER swelling and bleb formation which precede increases in cell membrane permeability after acute naphthalene injury to bronchiolar Clara cells in vivo.
Am J Respir Cell Mol Biol 1999 Jul
PMID:Early events in naphthalene-induced acute Clara cell toxicity: comparison of membrane permeability and ultrastructure. 1038 92

The guanidine-hydrochloride (Gdn-HCl) induced unfolding and refolding characteristics of the co-chaperonin GroES from Escherichia coli, a homoheptamer of subunit molecular mass 10,000 Da, were studied by using intrinsic fluorescence, 1-anilino-8-naphthalene sulfonate (ANS) binding, and size-exclusion HPLC. When monitored by tyrosine fluorescence, the unfolding reaction of GroES consisted of a single transition, with a transition midpoint at around 1.0 M Gdn-HCl. Interestingly, however, ANS binding and size-exclusion HPLC experiments strongly suggested the existence of an intermediate state in the transition. In order to confirm the existence of an intermediate state between the native heptameric and unfolded monomeric states, a tryptophan residue was introduced into the interface of GroES subunits as a fluorescent probe. The unfolding reaction of GroES I48W as monitored by tryptophyl fluorescence showed a single transition curve with a transition midpoint at 0.5 M Gdn-HCl. This unfolding transition curve as well as the refolding kinetics were dependent on the concentration of GroES protein. CD spectrum and size-exclusion HPLC experiments demonstrated that the intermediates assumed a partially folded conformation at around 0.5 M Gdn-HCl. The refolding of GroES protein from 3 M Gdn-HCl was probed functionally by measuring the extent of inhibition of GroEL ATPase activity and the enhancement of lactate dehydrogenase refolding yields in the presence of GroEL and ADP. These results clearly demonstrated that the GroES heptamer first dissociated to monomers and then unfolded completely upon increasing the concentration of Gdn-HCl, and that both transitions were reversible. From the thermodynamic analysis of the dissociation reaction, it was found that the partially folded monomer was only marginally stable and that the stability of GroES protein is governed mostly by the association of the subunits.
J Mol Biol 1999 Aug 20
PMID:Unfolding and refolding of Escherichia coli chaperonin GroES is expressed by a three-state model. 1044 48

The effects of fluoxetine on the oxidative phosphorylation of mitochondria isolated from rat brain and on the kinetic properties of submitochondrial particle F1F0-ATPase were evaluated. The state 3 respiration rate supported by pyruvate + malate, succinate, or ascorbate + tetramethyl-p-phenylenediamine (TMPD) was substantially decreased by fluoxetine. The IC50 for pyruvate + malate oxidation was approximately 0.15 mM and the pattern of inhibition was the typical one of the electron-transport inhibitors, in that the drug inhibited both ADP- and carbonyl cyanide m-chlorophenylhydrazone (CCCP)-stimulated respirations and the former inhibition was not released by the uncoupler. Fluoxetine also decreased the activity of submitochondrial particle F1F0-ATPase (IC50 approximately 0.08 mM) even though K0.5 and activity of Triton X-100 solubilized enzyme were not changed substantially. As a consequence of these effects, fluoxetine decreased the rate of ATP synthesis and depressed the phosphorylation potential of mitochondria. Incubation of mitochondria or submitochondrial particles with fluoxetine under the conditions of respiration or F1F0-ATPase assays, respectively, caused a dose-dependent enhancement of 1-anilino-8-naphthalene sulfonate (ANS) fluorescence. These results show that fluoxetine indirectly and nonspecifically affects electron transport and F1F0)-ATPase activity inhibiting oxidative phosphorylation in isolated rat brain mitochondria. They suggest, in addition, that these effects are mediated by the drug interference with the physical state of lipid bilayer of inner mitochondrial membrane.
Mol Cell Biochem 1999 Sep
PMID:Fluoxetine interacts with the lipid bilayer of the inner membrane in isolated rat brain mitochondria, inhibiting electron transport and F1F0-ATPase activity. 1054 58

Pseudomonas putida BS202 degrades naphthalene via a plasmid-encoded catabolic pathway. The nucleotide sequence of the nahC gene encoding one of this pathway enzymes, 1,2-dihydroxynaphthalene dioxygenase, has been determined. Analysis of nucleotide sequence of its flanking regions identified partially the nahF and putative nahQ genes. Comparison of these three genes with corresponding ones in the NAH7 plasmid and DOX operon showed a high degree of homology.
Mol Gen Mikrobiol Virusol 1999
PMID:Identification of nah-1 genes of the Pseudomonas putida naphthalene-degrading NPL-41 plasmid operon. 1062 37


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