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1.
Nat Commun ; 11(1): 235, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932585

RESUMO

Topological superconductors have attracted wide-spreading interests for the bright application perspectives to quantum computing. Cu0.3Bi2Se3 is a rare bulk topological superconductor with an odd-parity wave function, but the details of the vector order parameter d and its pinning mechanism are still unclear. Here, we succeed in growing CuxBi2Se3 single crystals with unprecedented high doping levels. For samples with x  = 0.28, 0.36 and 0.37 with similar carrier density as evidenced by the Knight shift, the in-plane upper critical field Hc2 shows a two-fold symmetry. However, the angle at which the Hc2 becomes minimal is different by 90° among them, which indicates that the d-vector direction is different for each crystal likely due to a different local environment. The carrier density for x  = 0.46 and 0.54 increases substantially compared to x ≤ 0.37. Surprisingly, the in-plane Hc2 anisotropy disappears, indicating that the gap symmetry undergoes a transition from nematic to isotropic (possibly chiral) as carrier increases.

2.
J Phys Condens Matter ; 32(17): 175703, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31923904

RESUMO

We report here the superconducting properties of a Laves phase superconductor SrIr2, which has a cubic MgCu2 structure. SrIr2 is a type-II superconductor, with a T c of 5.9 K. The estimated superconducting parameters of lower critical field µ 0 H c1 and upper critical field µ 0 H c2, coherence length ξ(0), penetration depth λ(0) and Ginzburg-Landau (GL) parameter κ(0) are approximately µ 0 H c1 = 101 Oe, µ 0 H c2(0) = 5.9 T, ξ(0) = 7.47 nm, λ(0) = 237 nm, and κ(0) = 31.7, respectively. The specific-heat data indicate that SrIr2 is a strong-coupling superconductor because the value of ΔC/γT c is approximately 1.71, which is larger than the value of 1.43 that is expected from the BCS theory. The physical properties obtained in this study are explained well by theoretical calculations including spin-orbit coupling (SOC). This result indicates that the physical properties of SrIr2 are strongly affected by the presence of SOC.

3.
Sci Rep ; 6: 27646, 2016 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-27276997

RESUMO

Recently, ammonia-thermal reaction has been used for molecular intercalation in layered FeSe, resulting a new Lix(NH3)yFe2Se2 superconductor with Tc ~ 45 K. Here, we have used temperature dependent extended x-ray absorption fine structure (EXAFS) to investigate local atomic displacements in single crystals of this new superconductor. Using polarized EXAFS at Fe K-edge we have obtained direct information on the local Fe-Se and Fe-Fe bondlengths and corresponding mean square relative displacements (MSRD). We find that the Se-height in the intercalated system is lower than the one in the binary FeSe, suggesting compressed FeSe4 tetrahedron in the title system. Incidentally, there is hardly any effect of the intercalation on the bondlengths characteristics, revealed by the Einstein temperatures, that are similar to those found in the binary FeSe. Therefore, the molecular intercalation induces an effective compression and decouples the FeSe slabs. Furthermore, the results reveal an anomalous change in the atomic correlations across Tc, appearing as a clear decrease in the MSRD, indicating hardening of the local lattice mode. Similar response of the local lattice has been found in other families of superconductors, e.g., A15-type and cuprates superconductors. This observation suggests that local atomic correlations should have some direct correlation with the superconductivity.

4.
J Food Sci Technol ; 52(9): 5772-80, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26344991

RESUMO

Fish meal has been used as an additional nitrogen source and fish oil as inducer for the growth and production of lipase from Cryptococcus sp. MTCC 5455. A response surface design illustrated that the optimum factors influencing lipase production were fish meal, 1.5 %, w/v, Na2HPO4, 0.2 %, w/v, yeast extract, 0.25 %, w/v and sardine oil, 2.0 %, w/v with an activity of 71.23 U/mL at 96 h and 25 °C, which was 48.39 % higher than the conventional one-factor-at-a-time method. The crude concentrated enzyme hydrolyzed polyurethane (PUR) efficiently and hydrolysis was 94 % at 30 °C and 96 h. The products, diethylene glycol and adipic acid were quantified by HPLC and scanning electron microscopic studies of the degraded polymer showed significant increase in size of the holes from 24 to 72 h of incubation. Hydrolysis of PUR within 96 h makes the lipase novel for disposal of PUR and provides an innovative solution to the problems created by plastic wastes.

5.
Bioresour Technol ; 101(17): 6791-6, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20400303

RESUMO

A novel tri-substrate fermentation (TSF) process was developed for the production of lipase from Aspergillus niger MTCC 2594 using agro-industrial residues, wheat bran (WB), coconut oil cake (COC) and an agro-product, wheat rawa (WR). The lipase activity was 628.7+/-13 U/g dry substrate (U/gds) at 30 degrees C and 96 h and growth studies indicated that addition of WR significantly augmented the biomass and lipase production. Scale up of lipase production at 100g and 3 kg (3 x 1 kg) tray-level batch fermentation resulted in 96% and 83.0% of enzyme activities, respectively, at 72 h. Maximum activity of 745.7+/-11U/gds was obtained, when fermented substrate was extracted in buffer containing 1% (w/v) sodium chloride and 0.5% (w/v) Triton X-100. Furthermore, the direct application of fermented substrate for tallow hydrolysis makes the process economical for industrial production of biofuel.


Assuntos
Aspergillus niger/enzimologia , Gorduras/metabolismo , Fermentação , Lipase/biossíntese , Biomassa , Hidrólise , Especificidade por Substrato
6.
J Cosmet Sci ; 56(1): 29-46, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15744439

RESUMO

The advantages and disadvantages of oxidative permanent and acid-type semi-permanent hair colors are evident. The former provides a longlasting "permanent" color, while the latter imparts less damage to the hair. We developed a novel acid-type hair color technology that can allow an acid dye and a metal ion to form a complex inside the hair similar to the oxidative hair color. It is well known that acid dye diffuses into the hair and creates an ionic bond with the positively charged amino acid residues of hair protein. However, the dye can be extracted easily from the hair by daily shampooing due to the weakness of the bond. In order to strengthen this bond and to prevent the extraction of the dye by shampooing, an aluminum chloride ion was chosen as the metal ion component to form the dye-metal complex. A proper composition of penetration enhancers, benzyl alcohol and ethyl alcohol, was required to allow acid dyes to interact with the aluminum chloride ion after each component penetrates deeply into the hair to form a complex inside the hair. To provide color brightness and a color longevity effect to hair color, glycolic acid was also selected due to the observation that a weak acid with a small molecular weight would enhance those effects.


Assuntos
Ácidos/química , Tinturas para Cabelo/química , Metais/química , Espectroscopia de Ressonância Magnética
7.
Appl Microbiol Biotechnol ; 64(6): 840-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-14727091

RESUMO

To obtain a novel matrix metalloproteinase (MMP) inhibitor produced by bacteria, we have focused on the chelating activity of siderophores. Several siderophore-producing bacteria were isolated from soil using chrome azurol S agar plates and then the effect of siderophores on MMP-2 activity was assayed by gelatin zymography. The results showed that partially purified siderophores from ten isolated strains inhibited MMP-2 activity. Among these strains, two were non-fluorescent and eight were fluorescent Pseudomonas species. From these eight strains, pyoverdine-type siderophores were detected. The Zn(2+)-chelating activity of these siderophores correlated with the inhibition of MMP-2 activity. Therefore, it is considered that siderophores such as pyoverdines inhibit MMP-2 activity by chelating Zn(2+) on the active site of MMP-2.


Assuntos
Inibidores de Metaloproteinases de Matriz , Pseudomonas/metabolismo , Sideróforos/farmacologia , Sítios de Ligação , Cromatografia Líquida , Hidroxibenzoatos , Metaloproteinase 2 da Matriz/metabolismo , Oligopeptídeos/biossíntese , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Pseudomonas/isolamento & purificação , Sideróforos/biossíntese , Sideróforos/isolamento & purificação , Microbiologia do Solo , Espectrometria de Massas por Ionização por Electrospray , Zinco/química
8.
Cell Mol Life Sci ; 61(1): 49-68, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14704853

RESUMO

In recent years, a number of mammalian zinc transporters have been identified, and candidate genes are rapidly growing. These transporters are classified into two families: ZIP (ZRT, IRT-like protein) and CDF (cation diffusion facilitator). ZIP members facilitate zinc influx into the cytosol, while CDF members facilitate its efflux from the cytosol. Molecular characterization of the transporters has brought about major advances in our understanding of their physiological functions. Zinc metabolism is regulated primarily through zinc-dependent control of transcription, translation, and intracellular trafficking of transporters. Analyses of mice whose zinc transporter genes have been genetically disrupted and of the naturally occurring mutant mice with symptoms related to abnormal zinc metabolism have provided compelling evidence that some zinc transporters play critical roles in zinc homeostasis. In this review, we review the literature of mammalian zinc transporters with emphasis on very recent findings and elicit integrative knowledge of zinc homeostasis.


Assuntos
Proteínas de Transporte/fisiologia , Animais , Transporte Biológico , Membrana Celular/metabolismo , Citoplasma/metabolismo , Homeostase , Humanos , Mamíferos , Modelos Biológicos , Zinco/metabolismo
9.
Biotechnol Lett ; 25(1): 23-8, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12882301

RESUMO

Microorganisms isolated from soil samples were screened for their ability to degrade various biodegradable polyester-based plastics. The most active strain, designated as strain TB-13, was selected as the best strain for degrading these plastics. From its phenotypic and genetic characteristics, strain TB-13 was closely related to Paenibacillus amyloyticus. It could degrade poly(lactic acid), poly(butylene succinate), poly(butylene succinate-co-adipate), poly(caprolactone) and poly(ethylene succinate) but not poly(hydroxybutylate-co-valerate). However, it could not utilize these plastics as sole carbon sources. Both protease and esterase activities, which may be involved in the degradation of plastic, were constitutively detected in the culture broth.


Assuntos
Bactérias Aeróbias/isolamento & purificação , Bactérias Aeróbias/metabolismo , Plásticos/metabolismo , Poliésteres/metabolismo , Microbiologia do Solo , Adipatos/metabolismo , Bactérias Aeróbias/classificação , Bactérias Aeróbias/fisiologia , Biodegradação Ambiental , Endopeptidases/metabolismo , Esterases/metabolismo , Ácido Láctico/metabolismo , Polímeros/metabolismo , Especificidade da Espécie , Succinatos/metabolismo
10.
Brain Res Bull ; 56(1): 23-8, 2001 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11604244

RESUMO

Brain renin-angiotensin system plays an important role in blood pressure regulation and is suggested to play a role in the development and maintenance of hypertension. To test the hypothesis that brain renin may play a significant role in hypertension in spontaneously hypertensive rats (SHR), phosphorothioated antisense oligodeoxynucleotides targeted to renin mRNA were administered intracerebroventricularly in SHR. Administration of an antisense but not its sense oligodeoxynucleotide produced a prolonged duration of decrease in blood pressure. Intra-arterial administration of the antisense oligodeoxynucleotide at the same dose that decreased blood pressure when administered intraventricularly did not affect blood pressure. Furthermore, renin mRNA but not angiotensin AT1 receptor mRNA levels were decreased in the hypothalamus of the antisense oligodeoxynucleotide-treated rats. These results suggest that brain renin may play a significant role in hypertension in SHR.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Encéfalo/metabolismo , Hipertensão/metabolismo , Oligodesoxirribonucleotídeos Antissenso/farmacologia , RNA Mensageiro/metabolismo , Ratos Endogâmicos SHR/metabolismo , Renina/genética , Animais , Pressão Sanguínea/fisiologia , Encéfalo/efeitos dos fármacos , Hipertensão/fisiopatologia , Injeções Intraventriculares , Masculino , RNA Mensageiro/antagonistas & inibidores , Ratos , Ratos Endogâmicos WKY/metabolismo , Receptor Tipo 1 de Angiotensina , Receptores de Angiotensina/genética
11.
J Hum Genet ; 46(10): 566-71, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11587069

RESUMO

Glutamine:fructose-6-phosphate amidotransferase (GFAT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in hyperglycemia-induced insulin resistance. To evaluate the role of GFAT1 expression, we analyzed the expression profiles of GFAT1 mRNA in various human tissues using reverse transcriptase-polymerase chain reaction. We report here the identification and cDNA cloning of a novel GFAT1 splice variant expressed abundantly in skeletal muscle and heart. This subtype, designated GFAT1-L, contains a 54-bp insertion within the GFAT1 coding sequence. Recombinant GFAT1-L protein possessed functional GFAT activities and biochemical characteristics similar to GFAT1. Previously, GFAT1 was considered a simplex enzyme. The identification of a novel GFAT1 subtype possessing functional enzymatic activity and tissue-specific expression should provide additional insight into the mechanism of skeletal muscle insulin resistance and diabetes complications.


Assuntos
Processamento Alternativo , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/biossíntese , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/química , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Músculo Esquelético/enzimologia , Sequência de Bases , Clonagem Molecular , DNA Complementar/metabolismo , Escherichia coli/metabolismo , Humanos , Cinética , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Isoformas de Proteínas , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência do Ácido Nucleico , Distribuição Tecidual
12.
Br J Pharmacol ; 134(4): 763-70, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11606316

RESUMO

1. Antagonistic properties of OPC-28326 ([4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl)] piperidine hydrochloride monohydrate), a selective peripheral vasodilator, were investigated by analysing the data from functional studies in various tissues from the rat and binding studies of the drug to alpha(2)-adrenoceptor subtypes. 2. Using a human recombinant receptor and rat kidney cortex, we found that OPC-28326 displays affinities to alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors with K(i) values of 2040, 285, and 55 nM, respectively. The K(i) values of yohimbine for alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenoceptors were 3.0, 2.0 and 11.0 nM, respectively. 3. B-HT 920, an alpha(2)-adrenoceptor agonist, produced a pressor response via peripheral postsynaptic alpha(2)-adrenoceptor stimulation (thought to be an alpha(2B)-subtype) in a reserpine-pretreated pithed rat preparation. OPC-28326 (3 - 30 mg kg(-1), i.v.) and yohimbine (0.3 - 3 mg kg(-1), i.v.) caused dose-dependent rightward shift in the pressor dose-response curve induced by B-HT 920. The apparent pA(2) values were 1.55 (0.87 - 2.75, 95% confidence interval) and 0.11 (0.06 - 0.21) mg kg(-1), respectively. The potency of OPC-28326 was about 14 times less than that of yohimbine. 4. Clonidine inhibited the tension developed by electrical stimulation, of the rat vas deferens, by its peripheral presynaptic alpha(2A/D)-adrenoceptor action. OPC-28326 (1 - 100 microM) and yohimbine (10 - 1000 nM) caused a rightward shift in the concentration-response curve of clonidine. The pA(2) values were 5.73 (5.54 - 5.91) and 7.92 (7.84 - 8.01), respectively, providing evidence for a potency of OPC-28326 of about 155 times less than that of yohimbine. 5. Mydriasis was induced by brimonidine via stimulation of central alpha(2A/D)-adrenoceptors in anaesthetized rats. Intravenous OPC-28326 had no effect on this action, even at a very high dose of 10 mg kg(-1) i.v., while yohimbine (0.1 - 0.3 mg kg(-1) i.v.) inhibited mydriasis in a dose-dependent manner, indicating that OPC-28326 was at least 100 times less potent than yohimbine in regard to the anti-mydriatic effect. 6. These data suggest that OPC-28326 preferentially exerts peripheral and postsynaptic antagonistic actions on the alpha(2B)- and alpha(2C)-adrenoceptor subtypes.


Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Compostos de Anilina/farmacologia , Piperidinas/farmacologia , Vasodilatadores/farmacologia , Antagonistas Adrenérgicos alfa/metabolismo , Compostos de Anilina/metabolismo , Animais , Azepinas/farmacologia , Ligação Competitiva , Pressão Sanguínea/efeitos dos fármacos , Tartarato de Brimonidina , Estado de Descerebração , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Midríase/induzido quimicamente , Midríase/prevenção & controle , Piperidinas/metabolismo , Quinoxalinas/administração & dosagem , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/fisiologia , Ioimbina/farmacologia
14.
Oncogene ; 20(34): 4718-27, 2001 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-11498794

RESUMO

We searched iron-deficient inducible cDNA, using subtraction cloning and mRNA from desferrioxamine-treated mouse macrophage Raw264.7 cells. We identified a pleomorphic adenoma gene like 2 (PLAGL2), one of PLAG superfamily proteins exhibiting antiproliferative properties on tumor cells. Mouse PLAGL2 consists of 496 amino acids with seven C2H2 zinc-fingers. PLAGL2 mRNA was induced in RAW264.7 cells, mouse erythroleukemia cells and Balb/c 3T3 cells when they were treated with desferrioxamine. Hypoxia also increased PLAGL2 mRNA. Expression of PLAGL2 in COS-7 cells led to nuclear localization. PLAGL2 had potential binding ability to GC-rich oligonucleotide and activated transcription of a gene with the binding sequence in transient reporter assay, a finding consistent with a case seen in a PLAGL2 homolog, ZAC-1. Transient co-transfection of PLAGL2 or ZAC1 cDNA and a reporter containing a lactate dehydrogenase A (LDHA) promoter carrying the hypoxia inducible factor-1 responsive element led to an increase in the basal transcription in Balb/c 3T3 and HepG2 cells. Activation in transcription from the LDHA promoter increased by desferrioxamine treatment or hypoxia was further enhanced when PLAGL2 was expressed. We propose that PLAGL2 is involved in the cell cycle arrest and apoptosis of tumor cells by regulating iron depletion- or hypoxia-inducible gene expression.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Genes Supressores de Tumor , Ferro/metabolismo , Proteínas de Ligação a RNA/fisiologia , Fatores de Transcrição , Sequência de Aminoácidos , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/fisiologia , Hipóxia Celular , Linhagem Celular , Núcleo Celular/metabolismo , Clonagem Molecular , Proteínas de Ligação a DNA/genética , Desferroxamina/farmacologia , Humanos , Fator 1 Induzível por Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Quelantes de Ferro/farmacologia , Isoenzimas/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares/genética , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA/genética , Elementos de Resposta , Homologia de Sequência de Aminoácidos , Transativadores/genética , Transativadores/fisiologia , Ativação Transcricional , Proteínas Supressoras de Tumor
15.
Cardiovasc Drug Rev ; 19(1): 1-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11314598

RESUMO

Pranidipine, a long acting 1,4-dihydropyridine calcium channel blocker, prolongs nitric oxide (NO)-mediated relaxation of rat aorta; it prolongs acetylcholine-induced relaxation in presence of endothelium as well as nitroglycerin-induced relaxation in absence of endothelium. In rat aorta the effect of pranidipine on NO-mediated relaxation is cyclic guanosine monophosphate (cGMP)-independent, but in guinea pig carotid artery the same effect of pranidipine is cGMP-dependent. It has been reported that in co-cultured human endothelial and smooth muscle cells pranidipine, at a higher concentration (10(-6) M), enhances vasorelaxant effect of NO by blocking NO decomposition. The enhancement of NO action by pranidipine differs from the direct NO-releasing action of other 1,4-dihydropyridines. It is expected that enhancement of NO-induced vasodilatation will lead to a venodilator action in vivo and less peripheral edema. The target organ protective effects of pranidipine are also reviewed in this article.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Óxido Nítrico/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Anlodipino/farmacologia , Animais , GMP Cíclico/metabolismo , Sinergismo Farmacológico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Humanos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Vasodilatação/fisiologia
16.
Eur J Pharmacol ; 411(1-2): 27-34, 2001 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-11137855

RESUMO

To examine whether angiotensin II and endothelins produced in vascular smooth muscle cells can play roles in the regulation of mitogen-activated protein (MAP) kinase activity in vascular smooth muscle cells, we measured the activity of MAP kinases in cultured vascular smooth muscle cells, and determined effects of renin-angiotensin and endothelin systems activators and inhibitors. Angiotensin II and endothelin-1 produced an activation of MAP kinase activity in vascular smooth muscle cells, whereas the angiotensin receptor antagonist, losartan and the endothelin receptor antagonist, cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl, BQ123) inhibited the enzyme activity. MAP kinase activity in vascular smooth muscle cells was also inhibited either by the renin inhibitor pepstatin A or by the angiotensin-converting enzyme inhibitor captopril. The degree of the inhibition of MAP kinase activity by pepstatin A, captopril and losartan was almost the same. Renin produced a considerable increase in MAP kinase activity and the renin-induced MAP kinase activation was inhibited by pepstatin A. The endothelin precursor big endothelin-1 produced an increase of MAP kinase activity in vascular smooth muscle cells, whereas the endothelin-converting enzyme inhibitor phosphoramidon inhibited the enzyme activity. These findings suggest that functional renin-angiotensin system and endothelin system are present in vascular smooth muscle cells and these systems tonically serve to increase MAP kinase activity. It appears that renin or renin-like substances play the determining role in the regulation of renin-angiotensin system in vascular smooth muscle cells.


Assuntos
Angiotensina II/fisiologia , Endotelinas/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/metabolismo , Angiotensina I/farmacologia , Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Captopril/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Antagonistas dos Receptores de Endotelina , Endotelina-1/farmacologia , Endotelinas/farmacologia , Glicopeptídeos/farmacologia , Losartan/farmacologia , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Pepstatinas/farmacologia , Peptídeos Cíclicos/farmacologia , Inibidores de Proteases/farmacologia , Precursores de Proteínas/farmacologia , Ratos , Ratos Wistar , Renina/farmacologia
17.
Biol Pharm Bull ; 23(11): 1379-81, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11085371

RESUMO

Blomhotin is a novel peptide (pGlu1-Gly2-Arg3-Pro4-Pro5-Gly6-Pro7-Pro8-Ile9-Pro10-Arg11) which has been isolated from the venom of Agkistrodon halys blomhoffii and exhibits contractile activity on rat stomach fundus. We carried out a structure-activity study of blomhotin and its related peptides, and the findings suggested that the N-terminal portion of blomhotin is mainly responsible for affinity for the blomhotin receptor, whereas the C-terminal portion of blomhotin, Pro-Ile-Pro-Arg, is responsible for complete activation of the blomhotin receptor in the rat stomach fundus. In particular, the amino acids at positions 9 and 11 of blomhotin appear to be essential for binding and intrinsic activity. Using knowledge gained from this structure-activity analysis, we have identified photoactive blomhotin analogues that have sufficient biological activity to probe the target molecule of blomhotin.


Assuntos
Venenos de Crotalídeos/farmacologia , Músculo Liso/efeitos dos fármacos , Animais , Venenos de Crotalídeos/agonistas , Venenos de Crotalídeos/química , Fundo Gástrico/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Marcadores de Fotoafinidade , Ácido Pirrolidonocarboxílico/análogos & derivados , Ratos , Ratos Wistar , Relação Estrutura-Atividade
18.
Blood ; 96(9): 3265-71, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11050012

RESUMO

We have previously reported that expression of the erythropoietin (Epo) gene in mouse embryonal cells was not induced by hypoxia, although hypoxia induced other hypoxia-inducible genes. This study identifies retinoic acid (RA) as an inducer for Epo production in the embryonal carcinoma cell lines P19 and F9. RA induced Epo production through the transcriptional activation of the Epo gene in an oxygen-independent manner. With the use of reporter assays in P19 cells, it is shown that a direct repeat of the nuclear hormone receptor-binding motif separated by a 2-bp spacer (DR-2) in the hypoxia-response enhancer was responsible for the transcriptional activation by RA. Electrophoretic mobility shift assays show that nuclear extracts from P19 cells contained RA receptor complexes that bound to DR-2. In human hepatoma Hep3B cells, an orphan receptor, hepatocyte nuclear factor-4, strongly augmented hypoxic induction of the Epo gene in cooperation with hypoxia-inducible factor-1 (HIF-1) by binding to DR-2, whereas in P19 cells, the interaction of RA receptors with DR-2 was sufficient for RA-induced transcriptional activation of the Epo gene without the requirement of the HIF-1 site. These results suggest that DR-2 regulates expression of the Epo gene by acting as the binding site for different transcription factors in different types of cells.


Assuntos
Carcinoma Embrionário/genética , Hipóxia Celular , Elementos Facilitadores Genéticos , Eritropoetina/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Receptores de Esteroides/metabolismo , Receptores dos Hormônios Tireóideos/metabolismo , Tretinoína/farmacologia , Animais , Sequência de Bases , Genes Reporter , Humanos , Luciferases/genética , Camundongos , Regiões Promotoras Genéticas , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Transfecção , Células Tumorais Cultivadas
19.
Eur J Pharmacol ; 400(2-3): 231-7, 2000 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-10988339

RESUMO

Regulation mechanisms of the activity of vascular mitogen-activated protein (MAP) kinases, enzymes believed to be involved in the pathway for cell proliferation, may be altered in hypertension. To examine whether vascular MAP kinase activation mechanisms are altered in hypertension, we measured the activity of MAP kinases in rat aorta strips from spontaneously hypertensive rats (SHR) and from deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and examined whether vascular angiotensin and endothelin systems are responsible for the alteration of MAP kinase activation in these hypertensive models. Endothelium-denuded aorta strips were incubated at 37 degrees C in medium. MAP kinase activity after incubation was increased in rat aorta strips. The MAP kinase activation was greater in 9- and 15-week-old SHR aorta strips than in age-matched Wistar Kyoto rats (WKY) aorta strips. Similarly, MAP kinase activation was enhanced in aorta strips from DOCA-salt hypertensive rats. In aorta strips from these kinds of rats, the angiotensin receptor antagonist, losartan, and the endothelin receptor antagonist, cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl) (BQ123), inhibited the MAP kinase activation. The losartan-induced, but not BQ123-induced, inhibition of MAP kinase activation was enhanced in 15-week-old SHR aorta strips, whereas the BQ123-induced, but not losartan-induced, inhibition of MAP kinase activation was enhanced in DOCA-salt hypertensive rat aorta strips. Angiotensin II-induced MAP kinase activation was enhanced in 15-week-old SHR aorta strips, whereas it was depressed in DOCA-salt hypertensive rat aorta strips. These results indicate that MAP kinase activation function is enhanced in aorta strips from both kinds of hypertensive rats. It appears that the enhancement of MAP kinase activation results partly from enhanced vascular angiotensin system in SHR and from enhanced vascular endothelin system in DOCA-salt hypertensive rats.


Assuntos
Hipertensão/enzimologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Músculo Liso Vascular/enzimologia , Angiotensina II/farmacologia , Antagonistas de Receptores de Angiotensina , Animais , Anti-Hipertensivos/farmacologia , Desoxicorticosterona , Antagonistas dos Receptores de Endotelina , Endotelina-1/farmacologia , Endotélio Vascular/fisiologia , Ativação Enzimática , Hipertensão/induzido quimicamente , Hipertensão/genética , Técnicas In Vitro , Losartan/farmacologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Peptídeos Cíclicos/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Wistar , Receptor Tipo 1 de Angiotensina , Receptor Tipo 2 de Angiotensina , Receptores de Angiotensina/fisiologia , Receptores de Endotelina/fisiologia , Cloreto de Sódio , Vasoconstritores/farmacologia
20.
Biochim Biophys Acta ; 1492(2-3): 493-8, 2000 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-10899588

RESUMO

Sphingomonas strain TZS-7 was reported as the first strain to have the ability to degrade 4,6-dimethyldibenzothiophene (4,6-dmDBT) by the ring-destructive pathway. Two genes for meta-cleavage dioxygenases were cloned from strain TZS-7. Expression of each gene showed that one enzyme was specific for 2,3-dihydroxybiphenyl while another was more specific for catechol. The genes for the two enzymes were named dmdC and catA. The analysis of deduced amino acid sequences indicates that CatA falls into the class of meta-cleavage dioxygenases acting on dihydroxylated monocyclic compounds and DmdC falls into the class of meta-cleavage dioxygenases acting on dihydroxylated polycyclic compounds.


Assuntos
Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Sphingomonas/genética , Sequência de Aminoácidos , Clonagem Molecular , Regulação Enzimológica da Expressão Gênica , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Tiofenos/metabolismo
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