Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 204
Filtrar
1.
Nat Commun ; 14(1): 3679, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37344458

RESUMO

Quantum spin liquid is a nontrivial magnetic state of longstanding interest, in which spins are strongly correlated and entangled but do not order; further intriguing is its doped version, which possibly hosts strange metal and unconventional superconductivity. A promising candidate of the doped spin liquid is a triangular-lattice organic conductor, κ-(BEDT-TTF)4Hg2.89Br8, recently found to hold metallicity, spin-liquid-like magnetism, and BEC-like superconductivity. The nature of the metallic state with the spin-liquid behaviour is awaiting to be further clarified. Here, we report the thermoelectric signature that mobile holes in the spin liquid background are in a quantum critical state and it pertains to the BEC-like superconductivity. The Seebeck coefficient divided by temperature, S/T, is enhanced on cooling with logarithmic divergence indicative of quantum criticality. Furthermore, the logarithmic enhancement is correlated with the superconducting transition temperature under pressure variation, and the temperature and magnetic field profile of S/T upon the superconducting transition change with pressure in a consistent way with the previously suggested BEC-BCS crossover. The present results reveal that the quantum criticality in a doped spin liquid emerges in a phase, not at a point, and is involved in the unconventional BEC-like nature.

2.
Phys Rev Lett ; 127(19): 197002, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34797153

RESUMO

Resonant optical excitation of certain molecular vibrations in κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Br has been shown to induce transient superconductinglike optical properties at temperatures far above equilibrium T_{c}. Here, we report experiments across the bandwidth-tuned phase diagram of this class of materials, and study the Mott insulator κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl and the metallic compound κ-(BEDT-TTF)_{2}Cu(NCS)_{2}. We find nonequilibrium photoinduced superconductivity only in κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Br, indicating that the proximity to the Mott insulating phase and possibly the presence of preexisting superconducting fluctuations are prerequisites for this effect.

3.
Nat Commun ; 12(1): 953, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574221

RESUMO

Ultrafast electronic-phase change in solids by light, called photoinduced phase transition, is a central issue in the field of non-equilibrium quantum physics, which has been developed very recently. In most of those phenomena, charge or spin orders in an original phase are melted by photocarrier generations, while an ordered state is usually difficult to be created from a non-ordered state by a photoexcitation. Here, we demonstrate that a strong terahertz electric-field pulse changes a Mott insulator of an organic molecular compound in κ-(ET)2Cu[N(CN)2]Cl (ET = bis(ethylenedithio)tetrathiafulvalene), to a macroscopically polarized charge-order state; herein, electronic ferroelectricity is induced by the collective intermolecular charge transfers in each dimer. In contrast, in an isostructural compound, κ-(ET)2Cu2(CN)3, which shows the spin-liquid state at low temperatures, a similar polar charge order is not stabilized by the same terahertz pulse. From the comparative studies of terahertz-field-induced second-harmonic-generation and reflectivity changes in the two compounds, we suggest the possibility that a coupling of charge and spin degrees of freedom would play important roles in the stabilization of polar charge order.

4.
Phys Chem Chem Phys ; 22(46): 27191-27205, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33226053

RESUMO

Domain-based local pair natural orbital (DLPNO) coupled cluster single and double (CCSD) with triple perturbation (T) correction methods were performed to elucidate the relative stabilities of ten different intermediate structures of the CaMn4Ox cluster in the S0 state of the oxygen evolving complex (OEC) of photosystem II (PSII). Full geometry optimizations of all the S0 intermediates were performed by the UB3LYP-D3/Def2-TZVP methods, providing the assumed geometrical structures and starting natural orbitals (UNO) for DLPNO-CCSD(T)/Def2TZVP calculations. The effective exchange integrals (J) for the spin Hamiltonian models for the ten intermediates were obtained by the UB3LYP/Def2-TZVP calculations followed by the general spin projections. DLPNO-CCSD(T) calculations followed by the CBS extrapolation procedure elucidated that the (II, III, IV, IV) and (III, III, III, IV) valence states in the CaMn4O5 cluster of the OEC of the PS II were nearly degenerated in energy in the S0 state, indicating an important role of dynamical electron correlation effects for the valence and spin fluctuations in strongly correlated electron systems (SCESs) consisting of 3d transition metals.


Assuntos
Cálcio/química , Manganês/química , Oxigênio/química , Complexo de Proteína do Fotossistema II/química , Proteínas de Bactérias/química , Teoria da Densidade Funcional , Modelos Químicos , Domínios Proteicos , Prótons , Termodinâmica , Thermosynechococcus/enzimologia
5.
Sci Adv ; 5(11): eaax8720, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763453

RESUMO

The concept of topology has been widely applied in condensed matter physics, leading to the identification of peculiar electronic states on three-dimensional (3D) surfaces or 2D lines separating topologically distinctive regions. In the systems explored so far, the topological boundaries are built-in walls; thus, their motional degrees of freedom, which potentially bring about new paradigms, have been experimentally inaccessible. Here, working with a quasi-1D organic material with a charge-transfer instability, we show that mobile neutral-ionic (dielectric-ferroelectric) domain boundaries with topological charges carry strongly 1D-confined and anomalously large electrical conduction with an energy gap much smaller than the one-particle excitation gap. This consequence is further supported by nuclear magnetic resonance detection of spin solitons, which are required for steady current of topological charges. The present observation of topological charge transport may open a new channel for broad charge transport-related phenomena such as thermoelectric effects.

6.
Nat Mater ; 18(3): 229-233, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30742081

RESUMO

Interparticle interactions are self-conflicting rather than cooperative on particular lattices. When such geometrical frustration occurs, charge ordering (CO) can be destabilized into non-trivial charge states such as the recently observed charge glass (CG). A more extreme case is the frustration-induced quantum melting of the CO that has been theoretically proposed. Here, we report d.c. charge transport and noise spectroscopy measurements for a triangular-lattice organic conductor situated close to the CO or CG. Our experiments demonstrate that these materials can host a strange metal with unusual charge dynamics, which we attribute to frustration-induced fluctuations of the CO or CG. Our results also show that the anomalous charge fluctuations can freeze into an insulating state when uniaxial stress is applied, which reduces the geometrical frustration. The present observations suggest the existence of the frustration-induced quantum melting of charges analogous to spin liquids.

7.
Sci Adv ; 4(11): eaau7725, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30515457

RESUMO

Topological defects have been explored in different fields ranging from condensed matter physics and particle physics to cosmology. In condensed matter, strong coupling between charge, spin, and lattice degrees of freedom brings about emergent excitations with topological characteristics at low energies. One-dimensional (1D) systems with degenerate dimerization patterns are typical stages for the generation of topological defects, dubbed "solitons"; for instance, charged solitons are responsible for high electrical conductivity in doped trans-polyacetylene. Here, we provide evidence based on a nuclear magnetic resonance (NMR) study for mobile spin solitons deconfined from a strongly charge-lattice-coupled spin-singlet ferroelectric order in a quasi-1D organic charge-transfer complex. The NMR spectral shift and relaxation rate associated with static and dynamic spin susceptibilities indicate that the ferroelectric order is violated by dilute solitonic spin excitations, which were further demonstrated to move diffusively by the frequency dependence of the relaxation rate. The traveling solitons revealed here may promise the emergence of anomalous electrical and thermal transport.

8.
Science ; 357(6358): 1378-1381, 2017 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-28963250

RESUMO

Interacting atoms or molecules condense into liquid, and, when cooled further, they form a crystal. The time evolution of the atomic or molecular ordering has been widely studied as a nonequilibrium emergence of order from a supercooled liquid or a glass. Interacting electrons in a variety of correlated electron systems also form crystals, but observing the time evolution of electronic crystallization has been experimentally challenging. Here, working with an organic conductor exhibiting a supercooled charge liquid or charge glass as a metastable state, we observed electronic crystal growth through resistivity and nuclear magnetic resonance measurements. The temperature profile of the crystal growth is similar to those observed in classical systems and reveals two distinct regimes for the mechanism of electronic crystallization.

9.
Nat Mater ; 16(11): 1100-1105, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28825731

RESUMO

The transition of a Mott insulator to metal, the Mott transition, can occur via carrier doping by elemental substitution, and by photoirradiation, as observed in transition-metal compounds and in organic materials. Here, we show that the application of a strong electric field can induce a Mott transition by a new pathway, namely through impulsive dielectric breakdown. Irradiation of a terahertz electric-field pulse on an ET-based compound, κ-(ET) 2Cu[N(CN) 2]Br (ET:bis(ethylenedithio)tetrathiafulvalene), collapses the original Mott gap of ∼30 meV with a ∼0.1 ps time constant after doublon-holon pair productions by quantum tunnelling processes, as indicated by the nonlinear increase of Drude-like low-energy spectral weights. Additionally, we demonstrate metallization using this method is faster than that by a femtosecond laser-pulse irradiation and that the transition dynamics are more electronic and coherent. Thus, strong terahertz-pulse irradiation is an effective approach to achieve a purely electronic Mott transition, enhancing the understanding of its quantum nature.

10.
J Bone Miner Metab ; 34(6): 615-626, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26475371

RESUMO

The lack of estrogen and inactivity are both important in the pathogenesis of osteoporosis in elderly women, and there have been no appropriate rodent studies to examine the effects of common bisphosphonates on these two components separately. We compared the efficacy of alendronate (ALN) on the long bones of aged female rats, which were sedentary, estrogen deficient, or both. The rats were either forced to remain in a sitting position or allowed to walk in standard cages with or without ALN administration. The 8-week experimental period began 5 weeks after ovariectomy or sham surgery. Parameters of the hindlimb bones were determined by a three-point bending test, peripheral quantitative computed tomography, microfocus computed tomography, confocal laser Raman microspectroscopy, and dynamic histomorphometry. Regardless of ovariectomy, ALN was ineffective against the deterioration of breaking stress caused by sitting even though the trabecular bone mineral density was significantly higher in the sitting-ALN groups. Toughness was significantly deficient in the ovariectomy sitting-ALN group. This was in agreement with the bone geometry with a greater marrow space. Sitting also increased the mineral-to-matrix ratio and the carbonate-to-phosphate ratio, both indicative of aged bone. A greater loss of proteinaceous amide intensity compared with mineral intensity resulted in an increased mineral-to-matrix ratio in the presence of ALN. Sitting resulted in deficits in the quality and the geometry of cortical bone, resulting in fragility. The use of bisphosphonates, such as ALN, may provide a therapy best suited for osteoporotic individuals whose daily activity is not limited.


Assuntos
Envelhecimento/metabolismo , Alendronato/farmacologia , Densidade Óssea/efeitos dos fármacos , Fraturas Ósseas/prevenção & controle , Imobilização , Envelhecimento/patologia , Animais , Feminino , Fraturas Ósseas/metabolismo , Fraturas Ósseas/patologia , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Wistar , Fatores de Tempo
11.
Phys Rev Lett ; 115(7): 077001, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26317741

RESUMO

Quantum spin liquids, which are spin versions of quantum matter, have been sought after in systems with geometrical frustration. We show that disorder drives a classical magnet into a quantum spin liquid through conducting NMR experiments on an organic Mott insulator, κ-(ET)_{2}Cu[N(CN)_{2}]Cl. Antiferromagnetic ordering in the pristine crystal, when irradiated by x rays, disappears. Spin freezing, spin gap, and critical slowing down are not observed, but gapless spin excitations emerge, suggesting a novel role of disorder that brings forth a quantum spin liquid from a classical ordered state.

12.
Phys Rev Lett ; 114(6): 067002, 2015 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-25723239

RESUMO

We report the pressure study of a doped organic superconductor with a Hall coefficient and conductivity measurements. We find that maximally enhanced superconductivity and a marginal-Fermi liquid appear around a certain pressure where mobile carriers increase critically, suggesting a possible quantum phase transition between strongly and weakly correlated regimes. This observation points to the presence of a criticality in Mottness for a doped Mott insulator with tunable correlation.

13.
Behav Brain Res ; 235(2): 318-25, 2012 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-22963996

RESUMO

Recent reports have implied that aberrant biochemical processes in the brain frequently accompany subtle shifts in the cellular epigenetic profile that might underlie the pathogenic progression of psychiatric disorders. Furthermore, certain antidepressants or mood stabilizers have been reported to have the ability to modulate epigenetic parameters. We previously reported that pretreatment of mice with 5-HT(1A) receptor agonists 24 h before testing suppressed the decrease in emotional behaviors induced by exposure to acute restraint stress. Based on this finding, the aim of the present study was to examine the association between the development of emotional resistance to stress stimuli and the modulation of an epigenetic parameter, particularly histone acetylation. We found that acetylated histone H3 was increased in the hippocampus of mice that had developed resistance to emotional stress by pretreatment with flesinoxan (1 mg/kg, i.p.) 24 h before testing. On the other hand, pretreatment with benzodiazepine anxiolytic diazepam (1 mg/kg, i.p.) did not have similar effects. Interestingly, similar to flesinoxan, the histone deacetylase inhibitor trichostatin A also protected against the emotional changes induced by acute restraint stress, as well as histone H3 acetylation. The present findings suggest that the epigenetic mechanisms of gene regulation may play an important role in the development of emotional resistance to stress stimuli.


Assuntos
Emoções/fisiologia , Epigênese Genética/fisiologia , Histonas/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Acetilação/efeitos dos fármacos , Análise de Variância , Animais , Ansiolíticos/uso terapêutico , Diazepam/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Interações Medicamentosas , Emoções/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos ICR , Piperazinas/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle , Fatores de Tempo
14.
Rev Sci Instrum ; 83(6): 064704, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22755648

RESUMO

A high-frequency NMR apparatus for use in pressure cell is described. All components of the resonance circuit are set in the pressure cell. This method makes the resonance frequency much less influenced by large stray capacitance residing at the electrical feedthrough of the pressure cell. With the use of this apparatus, a pressure-induced neutral-ionic phase transition in DMTTF-QBr(4) was successfully observed by (79)Br nuclear quadrupole resonance, whose resonance frequency is ∼300 MHz.

15.
Cancer Lett ; 293(1): 52-7, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20092938

RESUMO

Edaravone has been reported to have a radioprotective effect at high concentrations. We now report that a lower dose of edaravone enhanced X-ray-induced apoptosis of some cell lines harboring p53 wild-type status, such as MOLT-4, Nalm-6, and HepG2. The knock-down of p53 using siRNA in MOLT-4 cells abolished the radiosensitizing effect of edaravone. Enhanced phosphorylations of p53 at Ser 15 and Ser 20 and up-regulation of PUMA, a p53 target protein, were observed after X-irradiation in the presence of edaravone. We conclude that the low dose of edaravone sensitized cells to X-irradiation by promoting the p53-dependent apoptotic signaling pathway.


Assuntos
Antipirina/análogos & derivados , Apoptose/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Antipirina/farmacologia , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Edaravone , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Leucemia de Células T/tratamento farmacológico , Leucemia de Células T/metabolismo , Leucemia de Células T/patologia , Leucemia de Células T/radioterapia , Radiossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transfecção , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Raios X
16.
Neuroscience ; 161(2): 347-58, 2009 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-19303915

RESUMO

In line with previous studies using fMRI and as is apparent from experimental results, cerebral blood flow (oxygenated hemoglobin (oxyHb) concentration) in the medial prefrontal cortex (MPFC) and orbital cortex (OFC) as is observed with fNIRS (functional near-infrared spectroscopy) is presumed to be closely related to reward prediction and risk prediction as part of decision-making under risk. Results of analysis using a predictive model with a three-layer perceptron revealed that changes in the oxyHb concentration in cerebral blood as indicated by fNIRS observation include information to effectively predict investment behavior. This paper indicates that adding oxyHb concentration at the aforementioned sites in the brain as a predictive factor allows prediction of subjects' investment behavior with a considerable degree of precision. This fact indicates that information provided by fNIRS allows valid analysis of investment behavior and it also suggests a wide-ranging practical applicability for this information like investment assistance using fNIRS.


Assuntos
Técnicas de Apoio para a Decisão , Lobo Frontal/irrigação sanguínea , Investimentos em Saúde , Redes Neurais de Computação , Oxiemoglobinas/análise , Assunção de Riscos , Adolescente , Adulto , Teorema de Bayes , Circulação Cerebrovascular , Humanos , Córtex Pré-Frontal/irrigação sanguínea , Recompensa , Espectrofotometria Infravermelho , Adulto Jovem
17.
Osteoporos Int ; 20(11): 1863-72, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19280272

RESUMO

UNLABELLED: Prior 8-week treatment with menatetrenone, MK-4, followed by 8-week risedronate prevented the shortcomings of individual drugs and significantly increased the strength of ovariectomized ICR mouse femur compared to the ovariectomized (OVX) controls. Neither MK-4 following risedronate nor the concomitant administration may be recommended because they brought the least beneficial effect. INTRODUCTION: The objective of this study was to determine the best combinatory administration of risedronate at 0.25 mg/kg/day (R) with vitamin K(2) at approximately 100 microg MK-4/kg/day (K) to improve strength of osteoporotic mouse bone. METHODS: Thirteen-week-old ICR mice, ovariectomized at 9-week, were treated for 8 weeks with R, K, or R plus K (R/K), and then, either the treatment was withdrawn (WO) or switched to K or R in the case of R and K. After another 8 weeks, the mice were killed, and mechanical tests and analyses of femur properties by peripheral quantitative computed tomography, microfocus X-ray tube computed tomography, and confocal laser Raman microspectroscopy were carried out. RESULTS: The K to R femur turned out superior in parameters tested such as material properties, bone mineral density, BMC, trabecular structure, and geometry of the cortex. The increased cross-sectional moment of inertia, which occurred after K withdrawal, was prevented by risedronate in K to R. In addition to K to R, some properties of R to WO diaphysis and K to WO epiphysis were significantly better than OVX controls. CONCLUSION: Prior treatment with MK-4 followed by risedronate significantly increased femur strength in comparison to the OVX controls.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Ácido Etidrônico/análogos & derivados , Osteoporose/tratamento farmacológico , Vitamina K 2/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Ácido Etidrônico/administração & dosagem , Ácido Etidrônico/uso terapêutico , Feminino , Fêmur/patologia , Fêmur/fisiopatologia , Camundongos , Camundongos Endogâmicos ICR , Osteoporose/fisiopatologia , Ovariectomia , Ácido Risedrônico , Vitamina K 2/administração & dosagem , Vitamina K 2/uso terapêutico
18.
J Phys Condens Matter ; 21(1): 015602, 2009 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-21817227

RESUMO

Thermodynamic measurements on the organic system of (DI-DCNQI)(2)(Ag(1-x)Cu(x)) (x = 0,0.05, 0.71, 0.90) were performed to study the change from the charge-ordered (CO) insulating state to the π-d hybridized metallic state. A thermal anomaly associated with the antiferromagnetic transition that occurred in the charge-ordered lattice was observed at 6.2 K from the temperature dependence of the heat capacity of (DI-DCNQI)(2)Ag. We have found that the magnetic entropy around the peak is only 1.5% of Rln2, corresponding to the full entropy expected for the formula unit of (DI-DCNQI)(2)Ag. This anomaly is suppressed down to about 3 K in the x = 0.05 sample owing to the disorders induced in the CO lattice. In the metallic concentration of x = 0.90, the low-temperature electronic heat capacity coefficient, γ was found to be enhanced by up to about 63.6 mJ K(-2) mol(-1) probably owing to the cooperative effect of π-d hybridization and intersite Coulomb interaction (V).

19.
Anticancer Res ; 28(2B): 1169-79, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18505053

RESUMO

BACKGROUND: Regenerating gene type IV (RegIV) is a candidate marker for cancer and inflammatory bowel disease. In this study, its potential as a novel marker for the detection of gastric cancer peritoneal micrometastases was examined. PATIENTS AND METHODS: RegIV mRNA levels in the peritoneal washes of 95 gastric cancer patients and 22 with benign disease were quantified by real-time RT-PCR. To examine whether expression of RegIV enhance tumorigenicity or not, thirty two mice were injected intraperitoneally or subcutaneously with RegIV transfectants of TMK-1 cells, parental TMK-1 cells, or neomycin control transfectants. RESULTS: RegIV expression was markedly higher in patients with peritoneal metastases compared to those without. The level of RegIV mRNA in gastric cancer patients was related to the extent of wall penetration. A cut-off value for RegIV-positive expression was based on an analysis of negative control patients with benign disease, and gastric cancer patients above the cut-off value constituted the micrometastasis (MM+) group. Based on this criteria, 3 out of 43 T1 or T2 cases were MM+ (93% specificity). Among 15 patients with peritoneal dissemination (7 out of 15 cases were positive by cytology), 14 cases were positive for RegIV expression (93% sensitivity), while analysis of carcinoembryonic antigen (CEA) mRNA failed to detect micrometastases in 4 cases (73% sensitivity). Combined analysis of CEA and RegIV improved the accuracy of diagnosis to 100%. The prognosis of RegIV-positive cases was significantly worse than that of RegIV-negative cases. Multivariate analysis using the Cox proportional hazards model suggested that RegIV may be an independent prognostic factor. Stable expression of RegIV significantly enhanced peritoneal metastasis in an animal model of gastric cancer. CONCLUSION: These findings suggest that RegIV mRNA expression has the potential to serve as a novel marker for detecting peritoneal dissemination in gastric cancer.


Assuntos
Lectinas Tipo C/biossíntese , Actinas/biossíntese , Actinas/genética , Animais , Biomarcadores Tumorais , Antígeno Carcinoembrionário/biossíntese , Antígeno Carcinoembrionário/genética , Linhagem Celular Tumoral , Mucosa Gástrica/metabolismo , Mucosa Gástrica/fisiologia , Células HL-60 , Humanos , Lectinas Tipo C/genética , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Nus , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Proteínas Associadas a Pancreatite , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/secundário , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Transfecção
20.
Oncogene ; 27(13): 1930-8, 2008 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-17906693

RESUMO

Mitogen-activated protein kinases (MAPKs) are activated through the kinase cascades of MAPK, MAPK kinase (MAPKK) and MAPKK kinase (MAPKKK). MAPKKKs phosphorylate and activate their downstream MAPKKs, which in turn phosphorylate and activate their downstream MAPKs. MAPKKK proteins relay upstream signals through the MAPK cascades to induce cellular responses. However, the molecular mechanisms by which given MAPKKKs are regulated remain largely unknown. Here, we found that serine-threonine protein kinase 38, STK38, physically interacts with the MAPKKKs MEKK1 and MEKK2 (MEKK1/2). The carboxy terminus, including the catalytic domain, but not the amino terminus of MEKK1/2 was necessary for the interaction with STK38. STK38 inhibited MEKK1/2 activation without preventing MEKK1/2 binding to its substrate, SEK1. Importantly, STK38 suppressed the autophosphorylation of MEKK2 without interfering with MEKK2 dimer formation, and converted MEKK2 from its phosphorylated to its nonphosphorylated form. The negative regulation of MEKK1/2 was not due to its phosphorylation by STK38. On the other hand, stk38 short hairpin RNA enhanced sorbitol-induced activation of MEKK2 and phosphorylation of the downstream MAPKKs, MKK3/6. Taken together, our results indicate that STK38 negatively regulates the activation of MEKK1/2 by direct interaction with the catalytic domain of MEKK1/2, suggesting a novel mechanism of MEKK1/2 regulation.


Assuntos
Regulação da Expressão Gênica , MAP Quinase Quinase Quinase 1/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Animais , Western Blotting , Células COS , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/metabolismo , Chlorocebus aethiops , Dimerização , Perfilação da Expressão Gênica , Humanos , Imunoprecipitação , Indicadores e Reagentes/farmacologia , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase Quinase 1/genética , MAP Quinase Quinase Quinase 2 , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fosforilação , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , RNA Interferente Pequeno/farmacologia , Sorbitol/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...