Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Eur Respir J ; 38(2): 401-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21148224

RESUMO

Respiratory syncytial virus (RSV) causes bronchiolitis in young children and common colds in adults. There is no licensed vaccine, and prophylactic treatment with palivizumab is very expensive and limited to high-risk infants. Ribavirin is used as an antiviral treatment in infants and immunosuppressed patients, and its use is limited due to side-effects, toxicity to the recipient and staff, and evidence of marginal clinical efficacy. Therefore, we studied the in vivo kinetics, and the antiviral and protective properties of a novel candidate for RSV disease treatment. The drug is a small molecule (TMC353121) discovered by screening for fusion inhibitory properties against RSV in a cellular infection model. The pharmacokinetics of TMC353121 was studied in BALB/c mice and antiviral effects determined by testing viral loads in lung tissue by quantitative RT-PCR and plaque assay after intranasal RSV infection. At doses of 0.25-10 mg · kg(-1), TMC353121 significantly reduced viral load, bronchoalveolar lavage cell accumulation and the severity of lung histopathological change after infection. Treatment remained effective if started within 48 h of infection, but was ineffective thereafter. Therefore, TMC353121 is a novel potent antiviral drug, in vivo reducing RSV replication and inhibiting consequential lung inflammation, with a great potential for further clinical development.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Pulmão/efeitos dos fármacos , Piridinas/uso terapêutico , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/virologia , Feminino , Pulmão/virologia , Pneumopatias/tratamento farmacológico , Pneumopatias/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
2.
Clin Exp Metastasis ; 19(6): 465-76, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12405283

RESUMO

Tumor metastasis is responsible for a high degree of mortality in cancer patients. One of the genes involved in tumor metastasis is NM23. At present, eight human isoforms, transcribed from different NM23 genes, have been detected. The gene products have been identified as nucleoside diphosphate kinases (NDPKs), most of which catalyse the transfer of the gamma-phosphate of a (deoxy)nucleoside triphosphate to a (deoxy)nucleoside diphosphate. However, the function of NDPK isoforms involved in tumor metastasis cannot be explained on the basis of their phosphotransferase activity alone. At present, several other properties, like transcriptional regulation and protein kinase activity, have been assigned to these proteins. Moreover, it has also been shown that NDPKs interact with several other proteins, and binding partners of NDPKs are identified at an increasing rate. Accumulating evidence indicates that protein-protein interactions modulate the molecular action of NDPKs. In this review we provide a brief overview of how NDPKs are correlated with cancer, and discuss when and how the activities assigned to NDPKs may affect metastasis, with special emphasis on the role of protein-NDPK interactions in this process.


Assuntos
Proteínas Monoméricas de Ligação ao GTP/metabolismo , Metástase Neoplásica , Núcleosídeo-Difosfato Quinase/metabolismo , Fatores de Transcrição/metabolismo , Animais , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Monoméricas de Ligação ao GTP/genética , Nucleosídeo NM23 Difosfato Quinases , Fatores de Transcrição/genética , Transcrição Gênica
3.
J Neurochem ; 78(6): 1325-38, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11579141

RESUMO

We have previously shown that an ecto-NPPase modulates the ATP- and ADP-mediated P2Y(AC)-receptor activation in rat C6 glioma. In the present study, 2MeSADP and Ap(3)A induced no detectable PI turnover and were identified as specific agonists of the P2Y(AC)-receptor with EC(50) values of 250 +/- 37 pM and 1 +/- 0.5 microM, respectively. P2Y(AC)-receptor stimulation increased MAP kinase (ERK1/2) activation that returned to the basal level 4 h after stimulation and was correlated with a gradual desensitization of the P2Y(AC)-purinoceptor. The purinoceptor antagonists DIDS and RB2 blocked MAP kinase activation. An IP(3)-independent Ca(2+)-influx was observed after P2Y(AC)-receptor activation. Inhibition of this influx by Ca(2+)-chelation, did not affect MAP kinase activation. Pertussis toxin, toxin B, selective PKC-inhibitors and a specific MEK-inhibitor inhibited the 2MeSADP- and Ap(3)A-induced MAP kinase activation. In addition, transfection with dominant negative RhoA(Asn19) rendered C6 cells insensitive to P2Y(AC)-receptor-mediated MAP kinase activation whereas dominant negative ras was without effect. Immunoprecipitation experiments indicated a significant increase in the phosphorylation of raf-1 after P2Y(AC)-receptor activation. We may conclude that P2Y(AC)-purinoceptor agonists activate MAP kinase through a G(i)-RhoA-PKC-raf-MEK-dependent, but ras- and Ca(2+)-independent cascade.


Assuntos
Adenilil Ciclases/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Agonistas do Receptor Purinérgico P2 , Receptores Purinérgicos P2/metabolismo , Proteínas ras/fisiologia , Animais , Ativação Enzimática/efeitos dos fármacos , Toxina Pertussis , Proteína Quinase C/fisiologia , Antagonistas do Receptor Purinérgico P2 , Ratos , Células Tumorais Cultivadas , Fatores de Virulência de Bordetella/farmacologia , Proteína rhoA de Ligação ao GTP/fisiologia
4.
Br J Pharmacol ; 134(2): 402-8, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11564659

RESUMO

1. Extracellularly added P(1),P(3)-di(adenosine-5') triphosphate (Ap(3)A), P(1),P(4)-di(adenosine-5') tetraphosphate (Ap(4)A), ATP, ADP, AMP and adenosine are growth inhibitory for rat C6 glioma cells. Analysis of nucleotide hydrolysis and the use of nucleotidase inhibitors demonstrated that the latter inhibition is due to hydrolysis of the nucleotides to adenosine. 2. Agonists of the P2Y(AC)(-)-receptor enhance the growth of C6 cells if their hydrolysis to adenosine is inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). In these conditions, the potency to stimulate cell growth parallels the ranking of the receptor agonists, i.e. 2-methylthioadenosine-5'-diphosphate (2MeSADP)>Ap(3)A>Ap(4)A. ATP and ADP are still hydrolysed in the presence of PPADS and have no proliferative effect on C6 cells. 3. The enhanced growth is due to a P2Y(AC)(-)-receptor-mediated activation of p42/44 mitogen-activated protein kinase (MAPK) as shown by immunoblotting and protein kinase assays for active MAPK and the use of the MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitor PD98059. 4. The UTP-induced enhancement of the growth of C6 cells is due to activation of MAPK by a PPADS sensitive nucleotide receptor. 5. In conclusion, the effect of nucleotides on the growth of C6 cells is determined by ecto-nucleotidases and by activation of nucleotide receptors. Hydrolysis of nucleotides to adenosine induces growth inhibition while inhibition of the hydrolysis of agonists of the P2Y(AC)(-)-receptor enhances cell growth by activation of MAPK.


Assuntos
Difosfato de Adenosina/análogos & derivados , Divisão Celular/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Agonistas do Receptor Purinérgico P2 , Fosfato de Piridoxal/análogos & derivados , Adenosina/metabolismo , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/farmacologia , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Fosfatos de Dinucleosídeos/metabolismo , Fosfatos de Dinucleosídeos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Glioma/enzimologia , Glioma/patologia , Hidrólise , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfato de Piridoxal/farmacologia , Ratos , Receptores Purinérgicos P2/fisiologia , Tionucleotídeos/farmacologia , Fatores de Tempo , Triazinas/farmacologia , Células Tumorais Cultivadas
5.
Cell Biol Int ; 25(5): 467-74, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11401334

RESUMO

Glial fibrillary acidic protein (GFAP) is expressed upon cAMP-mediated induction of differentiation of glial progenitor cells into type II astrocytes. The protein is regulated by hormones, growth factors and cytokines but the signal transduction pathways involved in the regulation of GFAP expression are largely unknown. Specific protein kinase inhibitors were used to study their effect on the expression of GFAP in rat C6 glioma cells. Herbimycin A, a selective protein tyrosine kinase inhibitor, reduced GFAP mRNA and protein expression upon cAMP analog or beta-adrenergic receptor-mediated induction of differentiation. The latter inhibitor attenuated the elevation of cAMP by adenylate cyclase and abolished the activity of phosphatidylinositol 3-kinase (PI 3-K). These data indicate that GFAP expression is regulated by protein tyrosine phosphorylations, modulating the cAMP concentration and PI 3-K activity in C6 glioma cells.


Assuntos
Adenilil Ciclases/metabolismo , Proteína Glial Fibrilar Ácida/genética , Glioma , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Sulfonamidas , Agonistas Adrenérgicos beta/farmacologia , Androstadienos/farmacologia , Animais , Antibacterianos/farmacologia , Benzoquinonas , Diferenciação Celular/fisiologia , Cromonas/farmacologia , AMP Cíclico/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/fisiologia , Indóis/farmacologia , Isoproterenol/farmacologia , Isoquinolinas/farmacologia , Lactamas Macrocíclicas , Maleimidas/farmacologia , Morfolinas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinonas/farmacologia , Ratos , Rifabutina/análogos & derivados , Sirolimo/farmacologia , Células Tumorais Cultivadas , Wortmanina
6.
Eur J Biochem ; 268(3): 487-98, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11168386

RESUMO

Many cellular processes have been identified in which phosphatidylinositol 3-kinase has a key regulatory function. As an oncogene, it is also involved in the development of cancer. The transformation and progression of normal cells towards an advanced stage tumor and/or towards metastatic lesions involves a complex series of events, including genetic alterations, leading to aberrant cell cycle progression, altered adhesion and motility characteristics, inhibition of apoptosis and induction of angiogenesis. This review highlights the processes involved in the pathogenesis of cancer in which phosphatidylinositol 3-kinase is involved and provides an overview of the possible mechanisms by which the enzyme exerts its oncogenic action.


Assuntos
Neoplasias/enzimologia , Fosfatidilinositol 3-Quinases/fisiologia , Animais , Apoptose , Adesão Celular , Ciclo Celular , Divisão Celular , Sobrevivência Celular , Citoesqueleto/enzimologia , Progressão da Doença , Humanos , Camundongos , Modelos Biológicos , Invasividade Neoplásica , Metástase Neoplásica , Neovascularização Patológica , Células Tumorais Cultivadas
7.
J Neurochem ; 76(2): 610-8, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11208924

RESUMO

Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) protein expressed upon maturation of astrocytes and upregulated during reactive astrogliosis. Its expression is modulated by several growth factors and hormones. Although an upregulation of intracellular cAMP is required for the induction of GFAP expression in astrocytes, little information is available on other downstream factors of the signal transduction pathways involved in the regulation of its expression. In this communication, we identified phosphatidylinositol 3-kinase (PI 3-K) as a necessary enzyme for GFAP expression in rat C6 glioma cells. Use of the specific PI 3-K inhibitors wortmannin and LY294002 and transfection of C6 cells with a dominant negative PI 3-K construct, resulting in a decrease of the enzymatic activity of PI 3-K, inhibited the cAMP-dependent expression of GFAP. Furthermore, confocal laser scanning microscopy demonstrated that inhibition of the PI 3-K activity by LY294002 or wortmannin concomitant with induction of differentiation changes the cellular distribution leading to a pericentrosomal localization of GFAP and an altered cell shape lacking process formation. We conclude that the expression and cellular distribution of GFAP is mediated through a PI 3-K-dependent mechanism.


Assuntos
Diferenciação Celular/fisiologia , AMP Cíclico/metabolismo , Proteína Glial Fibrilar Ácida/biossíntese , Glioma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Bucladesina/farmacologia , Diferenciação Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Proteína Glial Fibrilar Ácida/genética , Inibidores de Fosfoinositídeo-3 Quinase , Transporte Proteico/efeitos dos fármacos , RNA Mensageiro/biossíntese , Ratos , Células Tumorais Cultivadas
8.
Exp Cell Res ; 262(2): 145-53, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11139339

RESUMO

Processes like cell proliferation, differentiation, and tumor metastasis require a flexible adaptation of cell shape and cell plasticity. A regulator of cell structure and shape is the centrosome and its associated microtubules. Recently, oncogenes like p53, pRB, and the tumor suppressor BRCA1 have been characterized as members of the centrosome. In this communication, we identified rat Nm23-R1/NDPKbeta, a homologue of the human tumor metastasis suppressor Nm23-H1 and a regulator of cell proliferation and differentiation, as a component of the centrosomal complex. We used confocal laser scanning microscopy on different cell types and biochemical analysis of purified centrosomes to demonstrate that Nm23-R1 is located in the centrosome of dividing and nondividing cells. We also showed that the centrosomal enzyme is catalytically active and able to transfer the gamma-phosphate from a nucleoside triphosphate to a nucleoside diphosphate. In addition, Nm23-R1 coimmunoprecipitated with gamma-tubulin, a core centrosomal protein essential for microtubule nucleation. In addition, human Nm23-R1/-H1 was also shown to be present in the centrosome of different human and rat cell types, demonstrating that the presence of Nm23-H1 homologues in the latter organelle is a general event.


Assuntos
Centrossomo/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Núcleosídeo-Difosfato Quinase/metabolismo , Fatores de Transcrição/metabolismo , Trifosfato de Adenosina/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Células Cultivadas , Centrossomo/química , Glioma/metabolismo , Guanosina Trifosfato/biossíntese , Imuno-Histoquímica , Isoenzimas/análise , Isoenzimas/metabolismo , Microtúbulos/metabolismo , Proteínas Monoméricas de Ligação ao GTP/análise , Nucleosídeo NM23 Difosfato Quinases , Metástase Neoplásica , Núcleosídeo-Difosfato Quinase/análise , Testes de Precipitina , Ratos , Proteínas Recombinantes/análise , Proteínas Recombinantes/metabolismo , Fatores de Transcrição/análise , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1 , Tubulina (Proteína)/metabolismo
9.
Exp Cell Res ; 261(1): 127-38, 2000 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-11082283

RESUMO

Nucleoside diphosphate kinases (Nm23/NDPK) are enzymes functional in cell proliferation, differentiation, development, tumor progression, and metastasis. Nevertheless, no consensus exists about the molecular mechanism by which Nm23/NDPK isoforms exert their role in these processes. We investigated the expression of the rat Nm23-R1/NDPKbeta and Nm23-R2/NDPKalpha isoforms, homologues of the human Nm23-H1/NDPK A and Nm23-H2/NDPK B proteins, respectively, upon cAMP-induced differentiation of rat C6 glioma cells and demonstrated a differential interaction with intermediate filaments. Semiquantitative RT-PCR, immunoblotting, and flow cytometry showed a constitutive expression of both Nm23 isoforms. After induction of differentiation in C6 cells with cAMP analogs or isoproterenol, a dose-dependent 2- and 2.5-fold upregulation of the Nm23-R1 mRNA and protein, respectively, was observed. In contrast, the expression of Nm23-R2 remained unchanged. Localization of both isoforms with confocal laser scanning microscopy demonstrated a punctate reticular staining pattern for both Nm23 isoforms in the cytosol and processes of the cells which was particularly intense in the perinuclear region. In addition, while Nm23-R2 was colocalized and coimmunoprecipitated with vimentin in nondifferentiated cells, both isoforms were associated with GFAP in differentiated cells. The significance of these findings in relation to a possible function of Nm23 isoforms in cell proliferation, differentiation, and tumor-associated mechanisms is discussed.


Assuntos
Diferenciação Celular/fisiologia , AMP Cíclico/fisiologia , Regulação Enzimológica da Expressão Gênica , Filamentos Intermediários/fisiologia , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Bucladesina/farmacologia , Citosol/enzimologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glioma , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Isoproterenol/farmacologia , Cinética , Nucleosídeo NM23 Difosfato Quinases , Núcleosídeo-Difosfato Quinase/genética , Núcleosídeo-Difosfato Quinase/metabolismo , Biossíntese de Proteínas , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Células Tumorais Cultivadas
10.
Br J Pharmacol ; 130(1): 139-45, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10781009

RESUMO

1. The effect of ecto-nucleotide pyrophosphatase (ecto-NPPase; EC 3.6.1. 9) on the ATP- and ADP-mediated receptor activation was studied in rat C6 glioma cells. The P2-purinoceptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and reactive blue (RB2) are potent inhibitors (IC(50)=12+/-3 microM) of the latter enzyme. 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS), 5'-phosphoadenosine 3'-phosphate (PAP) and suramin were less potent inhibitors with an IC(50) of 22+/-4, 36+/-7 and 72+/-11 microM respectively. 2. P1-purinoceptor antagonists CGS 15943, cyclo-pentyl theophylline (CTP) and theophylline did not affect the activity of the ecto-NPPase. 3. ATP- and ADP-mediated P2Y(1)-like receptor activation inhibited the (-)-isoproterenol-induced increase of intracellular cyclic AMP concentration. PPADS, an ineffective P2Y-antagonist in C6, potentiated the ATP and ADP effect approximately 3 fold due to inhibition of nucleotide hydrolysis by the ecto-NPPase. 4. We conclude that ecto-NPPase has a modulator effect on purinoceptor-mediated signalling in C6 glioma cell cultures.


Assuntos
Trifosfato de Adenosina/metabolismo , AMP Cíclico/metabolismo , Pirofosfatases/metabolismo , Receptores Purinérgicos P2/metabolismo , Animais , Inibidores da Agregação Plaquetária/farmacologia , Antagonistas do Receptor Purinérgico P2 , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Pirofosfatases/antagonistas & inibidores , Pirofosfatases/efeitos dos fármacos , Ratos , Receptores Purinérgicos P2Y1 , Transdução de Sinais , Células Tumorais Cultivadas
11.
J Neurochem ; 72(2): 826-34, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9930759

RESUMO

The presence of a nucleotide pyrophosphatase (EC 3.6.1.9) on the plasma membrane of rat C6 glioma has been demonstrated by analysis of the hydrolysis of ATP labeled in the base and in the alpha- and gamma-phosphates. The enzyme degraded ATP into AMP and PPi and, depending on the ATP concentration, accounted for approximately 50-75% of the extracellular degradation of ATP. The association of the enzyme with the plasma membrane was confirmed by ATP hydrolysis in the presence of a varying concentration of pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a membrane-impermeable inhibitor of the enzyme. PPADS concentration above 20 microM abolished the degradation of ATP into AMP and PPi. The nucleotide pyrophosphatase has an alkaline pH optimum and a Km for ATP of 17 +/- 5 microM. The enzyme has a broad substrate specificity and hydrolyzes nucleoside triphosphates, nucleoside diphosphates, dinucleoside polyphosphates, and nucleoside monophosphate esters but is inhibited by nucleoside monophosphates, adenosine 3',5'-bisphosphate, and PPADS. The substrate specificity characterizes the enzyme as a nucleotide pyrophosphatase/phosphodiesterase I (PD-I). Immunoblotting and autoadenylylation identified the enzyme as a plasma cell differentiation antigen-related protein. Hydrolysis of ATP terminates the autophosphorylation of a nucleoside diphosphate kinase (NDPK/nm23) detected in the conditioned medium of C6 cultures. A function of the pyrophosphatase/PD-I and NDPK in the purinergic and pyrimidinergic signal transduction in C6 is discussed.


Assuntos
Trifosfato de Adenosina/metabolismo , Espaço Extracelular/enzimologia , Glioma , Pirofosfatases/metabolismo , Animais , Astrócitos/química , Astrócitos/enzimologia , Inibidores Enzimáticos/farmacologia , Guanosina Trifosfato/metabolismo , Hidrólise , Núcleosídeo-Difosfato Quinase/antagonistas & inibidores , Núcleosídeo-Difosfato Quinase/metabolismo , Radioisótopos de Fósforo , Fosforilação , Inibidores da Agregação Plaquetária/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Ratos , Receptores Purinérgicos/fisiologia , Células-Tronco/química , Células-Tronco/enzimologia , Células Tumorais Cultivadas
12.
FEBS Lett ; 400(1): 75-9, 1997 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-9000516

RESUMO

Nucleoside diphosphate kinase (NDPK/nm23) ATP/GDP phosphotransferase activity and serine autophosphorylation is inhibited by N6-mbcAMP, 8-ClcAMP and 8-BrcAMP. Inhibition of the enzymatic activity largely depends on the concentration of ATP and becomes significant at ATP concentrations up to 0.5 mM and at effector concentrations measured in C6 cells stimulated with 1 mM cAMP analogue. N6-mbcAMP is a substrate of the enzyme. DbcAMP and 0'2-mbcAMP, cAMP analogues with a modified 0'2-ribose, did not affect the NDPK activity. Cyclic AMP is only a moderate inhibitor of NDPK even at low ATP concentrations. Possible inhibitory effects of cAMP and cAMP analogues on reported extra- and intracellular functions of NDPK/nm23 are discussed.


Assuntos
AMP Cíclico/análogos & derivados , Inibidores Enzimáticos/farmacologia , Proteínas Monoméricas de Ligação ao GTP , Núcleosídeo-Difosfato Quinase/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Animais , Divisão Celular , AMP Cíclico/farmacologia , Nucleosídeo NM23 Difosfato Quinases , Ratos , Células Tumorais Cultivadas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA