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1.
Rev. psicopatol. salud ment. niño adolesc ; (40): 111-128, Nov. 2022. ilus
Artigo em Espanhol | IBECS | ID: ibc-215086

RESUMO

Los padres que no lograron elaborar e integrar sus experiencias traumáticas ponen en peligro el desarrollo y la salud psíquica de sus hijos. La transmisión de los trastornos de regulación propia y de la relación dependientes del trauma se realiza a través de diferentes “correas de transmisión”. Los momentos atmosféricos, las fantasías, los sentimientos y las convicciones de los padres traumatizados, el tipo y la calidad de su modo de relacionarse, así como las interacciones concretas con los hijos hacen surgir lo traumático entre padres e hijos. Los procesos traumáticos perturban la capacidad de mentalización de los padres y dificultan o imposibilitan que los hijos consigan desarrollar adecuadamente su competencia mentalizadora. Las intervenciones psicoterapéuticas orientadas a la mentalización en diferentes modalidades (familiar, atención a los padres, individual) pueden ayudar a la elaboración y la resolución de los procesos de transmisión transgeneracional. En este artículo, las consideraciones teóricas se ilustran y acompañan con tres presentaciones de casos.(AU)


Parents who have not been able to process and integrate their traumatic experiences endanger the development and psychological health of their children. The transmission of trauma-dependent self-regulation and relationship disorders takes place via different "transmission belts". Atmospheric moments, fantasies, feelings, and convictions of the traumatised parents, the type and quality of their relationships as well as the concrete interactions with the children give rise to the trauma between parents and children. Traumatic processes disrupt the mentalising capacity of the parents and make it difficult or impossible for the children to develop their mentalising competence adequately. Mentalization-oriented psychotherapeutic interventions in different modalities (family, parenting, individual) can help in the elaboration and resolution of transgenerational transmission processes. In this article, theoretical considerations are illustrated and accompanied by three case presentations.(AU)


Els pares que no van aconseguir elaborar i integrar les seves experiències traumàtiques posen en perill el desenvolupament i la salut psíquica dels fills. La transmissió dels trastorns de regulació pròpia i de la relació dependents del trauma es realitza a través de diferents “corretges de transmissió”. Els moments atmosfèrics, les fantasies, els sentiments i les conviccions dels pares traumatitzats, el tipus i la qualitat de la seva manera de relacionar-se, així com les interaccions concretes amb els fills fan sorgir tot allò que és traumàtic entre pares i fills. Els processos traumàtics pertorben la capacitat de mentalització dels pares i dificulten o impossibiliten que els fills aconsegueixin desenvolupar adequadament la seva competència mentalitzadora. Les intervencions psicoterapèutiques orientades a la mentalització en diferents modalitats (familiar, atenció als pares, individual) poden ajudar a elaborar i resoldre els processos de transmissió transgeneracional. En aquest article, les consideracions teòriques s'il·lustren i acompanyen amb tres presentacions de casos.(AU)


Assuntos
Humanos , Masculino , Feminino , Teoria da Mente , Resiliência Psicológica , Transcrição Gênica , Pais , Mães , Trauma Psicológico , Psicoterapia , Saúde da Família
2.
Clin. transl. oncol. (Print) ; 23(6): 1105-1116, jun. 2021. graf
Artigo em Inglês | IBECS | ID: ibc-221331

RESUMO

Background Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular biology processes, for example, participate in chromatin remodeling, imprinting, splicing, transcriptional regulation and translation. Dysregulation of lncRNA expression is act as a feature of various diseases and cancers, including hematopoietic malignancies. However, the clinical relevance of myelodysplastic syndrome (MDS) and acute myeloid leukemia preceded by MDS (MDS-AML) requires further research. Recently, lncRNAs have been demonstrated, which play an important role in hematopoiesis, thus, to further finding more functional lncRNA seemed particularly important. Methods Western blotting, real-time PCR, RNA-pulldown, RIP (RNA immunoprecipitation), Chromatin immunoprecipitation (ChIP), cellular compartments extraction assays, SA-β-gal staining, lentivirus transfection, cell viability assay and cell proliferation assays were used to examine the relationship between lncRNA LINC01255 and its regulation of p53–p21 pathway in human mesenchymal stromal and acute myeloid leukemia cells. Results LncRNA LINC01255 is highly expressed in bone marrow cells of AML patients, CD34+ cells of MDS-AML patients and AML cell lines and the higher expression of LINC01255 is associated with poor survival rate of AML patients. LINC01255 can interact with BMI1 and repress the transcription of MCP-1 to active p53–p21 pathway, thus inhibiting the senescence of human mesenchymal stromal and proliferation of acute myeloid leukemia cell. Conclusions We discovered a novel functional lncRNA LINC01255, which can regulate the senescence of human mesenchymal stromal and the proliferation of acute myeloid leukemia cell through inhibiting the transcription of MCP-1 (AU)


Assuntos
Humanos , Proliferação de Células , Senescência Celular/genética , Quimiocina CCL2/genética , Leucemia Mieloide Aguda/patologia , Células-Tronco Mesenquimais/patologia , Complexo Repressor Polycomb 1/fisiologia , RNA Longo não Codificante/fisiologia , Células Tumorais Cultivadas , Transcrição Gênica
3.
Endocrinol. diabetes nutr. (Ed. impr.) ; 65(1): 52-59, ene. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-171915

RESUMO

El complejo de Carney es un síndrome de neoplasia múltiple de tumores endocrinos y no endocrinos, que incluye la presencia de mixoma, lentiginosis cutánea y enfermedad nodular primaria pigmentada, entre otros criterios para el diagnóstico. En la mayoría de los casos es de transmisión autosómica dominante, por lo que su diagnóstico hace necesario el estudio y seguimiento familiar. Se ha identificado la presencia de mutaciones inactivantes del gen PRKAR1A como causante de la enfermedad. Desde el año 2015 se han agregado otros genes relacionados, como variantes activantes del gen PRKACA y PRKACB. En este trabajo se ahondará en los aspectos genéticos relacionadas con el complejo de Carney (AU)


Carney complex is a multiple neoplasia syndrome having endocrine and non-endocrine manifestations. Diagnostic criteria include myxoma, lentigines, and primary pigmented nodular adrenocortical disease, amongst other signs/symptoms. In most cases it is an autosomal dominant disease, and diagnosis therefore requires study and follow-up of the family members. Inactivating mutations of the PRKAR1A gene were identified as the main cause of the disease, although since 2015 other disease-related genes, including PRKACA and PRKACB activating mutations, have also been related with Carney complex. This review will address the genetic aspects related to Carney complex (AU)


Assuntos
Humanos , Masculino , Feminino , Complexo de Carney/diagnóstico , Complexo de Carney/genética , Mixoma/complicações , Transcrição Gênica/genética , Complexo de Carney/complicações , Doença de Paget Mamária/epidemiologia
4.
J. physiol. biochem ; 70(4): 877-889, dic. 2014.
Artigo em Inglês | IBECS | ID: ibc-131422

RESUMO

REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which down regulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing


Assuntos
Animais , Ratos , Privação do Sono/fisiopatologia , Núcleos Ventrais do Tálamo/fisiopatologia , Modelos Animais de Doenças , Ratos Sprague-Dawley/fisiologia , Expressão Gênica/fisiologia , Nociceptividade/fisiologia , Transcrição Gênica
5.
Rev. esp. cir. ortop. traumatol. (Ed. impr.) ; 58(3): 138-143, mayo-jun. 2014. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-122523

RESUMO

Objetivo: Los miARN actúan como silenciadores génicos que están implicados en la regulación de funciones celulares esenciales. El miR-335 participa regulando los procesos de diferenciación celular en células progenitoras. Las células madre mesenquimales (MSC) son células progenitoras de los condrocitos y osteoblastos encargados del mantenimiento homeostático del cartílago y hueso. El objetivo de este estudio era determinar una posible asociación entre la expresión de miR-335 y la enfermedad artrósica. Metodología: Las MSC obtenidas de la médula ósea de 3 pacientes artrósicos y 3 controles sin signos clínicos de artrosis ni osteoporosis se cultivaron y caracterizaron fenotípica y funcionalmente en el pase 3 de cultivo. Así mismo, mediante PCR cuantitativa se determinaron los niveles de expresión de miR-335 y del gen mesoderm-specific transcript ---MEST---, que controla su expresión. Resultados: Se detectaron diferencias entre las MSC aisladas de pacientes con artrosis y los controles en los niveles de expresión de miR-335 y de MEST (mediana [rango intercuartílico]: 1,69 [0,85-1,74]; 3,85 [3,20-5,67]). Aunque las diferencias detectadas no alcanzaron una significación estadística (p = 0,1), sí se apreció una clara tendencia a una menor expresión de miR-335 en las MSC de pacientes artrósicos. Conclusiones: Teniendo en cuenta que miR-335 tiene como dianas potenciales diferentes genes que participan en la vía de se˜nalización de la Wnt, la tendencia observada podría determinar, al menos en parte, algunas de las alteraciones que determinan el inicio o progresión de la artrosis, y puede, por lo tanto, servir en el diseño de futuras dianas terapéuticas para el tratamiento de esta enfermedad (AU)


Objective: MiRNAs act as gene silencers that are involved in the regulation of essential cell functions. miR-335 is involved in regulating cell differentiation processes in progenitor cells. Mesenchymal stem cells (MSCs) are progenitor cells of chondrocytes and osteoblasts responsible for homeostatic maintenance of cartilage and bone. The aim of this study was to determine a possible relationship between the expression of miR-335 and osteoarthritis. Methods: MSCs obtained from the bone marrow of 3 osteoarthritic patients and 3 controls with no clinical signs of osteoarthritis or osteoporosis were cultured and phenotypically and functionally characterised in a 3-step culture. Expression levels of miR-335 and the mesodermspecific transcript gene ---MEST--- that controls its expression were determined by quantitative PCR. Results: Differences in the expression levels of miR-335 and MEST (median [interquartile range]: 1.69 [0.85-1.74], and 3.85 [3.20-5.67] were detected between MSCs isolated from patients with osteoarthritis and controls. Although the differences detected did not reach statistical significance (P = .1), a clear trend towards lower expression of miR-335 in osteoarthritis MSCs was observed. Conclusions: Given that miR-335 has the different genes involved in the Wnt signalling pathway as potential targets, the observed trend may help to ascertain, at least partially, some of the alterations which determine the onset or progression of osteoarthritis, and can therefore serve for the design of future therapeutic targets for the treatment of this disease (AU)


Assuntos
Humanos , MicroRNAs/fisiologia , Osteoartrite/fisiopatologia , Células-Tronco/fisiologia , Mesoderma/fisiologia , Inativação Gênica , Estudos de Casos e Controles , Transcrição Gênica/fisiologia
6.
Med. clín (Ed. impr.) ; 137(supl.1): 17-22, sept. 2011. graf
Artigo em Espanhol | IBECS | ID: ibc-141092

RESUMO

La enfermedad de Gaucher (EG) se debe a una deficiencia en la actividad de la enzima lisosomal glucocerebrosidasa y, en muy raras ocasiones, a un déficit de su activador, la saposina C. La complejidad de identificación y caracterización de las mutaciones en el gen de la glucocerebrosidasa (GBA1) radica en la alta diversidad de alelos mutados, en la presencia de un seudogén altamente homólogo y a su localización en una zona muy rica en genes, lo cual favorece la presencia de alelos complejos. Aunque las relaciones genotipofenotipo en EG no se hallan completamente establecidas, existe una serie de generalidades, como que la mutación c.1226A>G (N370S) posee cierto grado de neuroprotección y que la homocigosidad para la mutación c.1448T>C (L444P) cursa con sintomatología neurológica (AU)


Gaucher’s disease (GD) results from a deficiency of the lysosomal enzyme glucocerebrosidase and, in very rare occasions, a deficiency of its activator, the saposin C. The complexity of identification and characterization of mutations in the gene of glucocerebrosidase (GBA1) is caused by a great amount of mutated alleles, the existence of a highly homologous pseudogene and its location in a very rich zone in genes, which promotes the presence of complex alleles. Although genotype-phenotype correlations in EG are not completely established, there are a series of generalities, as the mutation c.1226A>G (N370S) is often associated with a certain degree of neuroproctetion and the homozygosity for the c.1448T>C (L444P) mutation presents with neurological symptoms (AU)


Assuntos
Humanos , Doença de Gaucher/enzimologia , Doença de Gaucher/genética , Estudos de Associação Genética , Glucosilceramidase/deficiência , Glucosilceramidase/genética , Mutação/genética , Alelos , Taxa de Mutação , Polimorfismo Genético , Saposinas/genética , Transcrição Gênica
7.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 36(5): 273-277, mayo 2010. ilus
Artigo em Espanhol | IBECS | ID: ibc-79947

RESUMO

El ADN es «la molécula de la vida», y es la que lleva codificada la información genética característica de los diferentes seres vivos. Mediante ese código, regula el funcionamiento de cada tipo de célula; controla la transmisión de esa información, tanto en el tiempo como en el lugar de actuación de la misma; coordina la complejísima red de interacciones del funcionamiento celular y tisular; controla también su propia duplicación, reparación y autorregulación. Igualmente, controla y coordina los procesos de reproducción y mantenimiento de las características de cada especie. Todas estas actividades funcionales son reguladas y conducidas por un conjunto de instrucciones que constituyen el llamado código genético. El resultado se basa en un equilibrio entre la influencia del ambiente y esta compleja red funcional del ADN que muestra, además, un muy alto grado de plasticidad. Por ello, el genoma puede producir respuestas adecuadas a diferentes cambios del ambiente, manteniendo ese equilibrio. No obstante, a pesar de la importante capacidad homeostática del genoma, es susceptible de sufrir alteraciones por ciertos agentes que modifican el ambiente, dando lugar a efectos adversos y patológicos (AU)


The DNA is the “molecule of life,” and is that which carries the coded genetic information of the different human beings. Through this code, the functioning of each type of cell is regulated. It controls the transmission of this information, both in its time and place of action. It coordinates the very complex network of interactions of the cell and tissue function. It also controls its own replication, repair and self-regulation. Furthermore, it controls and coordinates the reproduction and maintenance processes of the characteristics of each species. All these functional activities are regulated and conducted through a combination of instructions that make up the so-called genetic code. The result is based on a balance between environmental influence and this complex functional network of the DNA that also shows a very high plasticity grade. Thus, the genome can produce adequate responses to different environmental changes, maintaining this balance. However, in spite of the important hemostatic capacity of the genome, it can be altered by some agents that modify the environment, giving rise to adverse effects and pathologic conditions (AU)


Assuntos
Humanos , DNA/ultraestrutura , Genes/fisiologia , Mutação/fisiologia , Código Genético , Predisposição Genética para Doença , DNA/fisiologia , RNA Mensageiro/ultraestrutura , Transcrição Gênica
8.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. impr.) ; 36(4): 273-277, abr. 2010. ilus
Artigo em Espanhol | IBECS | ID: ibc-79425

RESUMO

El ADN es «la molécula de la vida», y es la que lleva codificada la información genética característica de los diferentes seres vivos. Mediante ese código, regula el funcionamiento de cada tipo de célula; controla la transmisión de esa información, tanto en el tiempo como en el lugar de actuación de la misma; coordina la complejísima red de interacciones del funcionamiento celular y tisular; controla también su propia duplicación, reparación y autorregulación. Igualmente, controla y coordina los procesos de reproducción y mantenimiento de las características de cada especie. Todas estas actividades funcionales son reguladas y conducidas por un conjunto de instrucciones que constituyen el llamado código genético. El resultado se basa en un equilibrio entre la influencia del ambiente y esta compleja red funcional del ADN que muestra, además, un muy alto grado de plasticidad. Por ello, el genoma puede producir respuestas adecuadas a diferentes cambios del ambiente, manteniendo ese equilibrio. No obstante, a pesar de la importante capacidad homeostática del genoma, es susceptible de sufrir alteraciones por ciertos agentes que modifican el ambiente, dando lugar a efectos adversos y patológicos (AU)


The DNA is the “molecule of life,” and is that which carries the coded genetic information of the different human beings. Through this code, the functioning of each type of cell is regulated. It controls the transmission of this information, both in its time and place of action. It coordinates the very complex network of interactions of the cell and tissue function. It also controls its own replication, repair and self-regulation. Furthermore, it controls and coordinates the reproduction and maintenance processes of the characteristics of each species. All these functional activities are regulated and conducted through a combination of instructions that make up the so-called genetic code. The result is based on a balance between environmental influence and this complex functional network of the DNA that also shows a very high plasticity grade. Thus, the genome can produce adequate responses to different environmental changes, maintaining this balance. However, in spite of the important hemostatic capacity of the genome, it can be altered by some agents that modify the environment, giving rise to adverse effects and pathologic conditions (AU)


Assuntos
Humanos , DNA/ultraestrutura , Código Genético , Mutação , Desoxigenação Nitrogenada , Transcrição Gênica , Genoma Humano
11.
Rev. esp. cardiol. Supl. (Ed. impresa) ; 9(supl.B): 14b-23b, 2009. graf, ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-166430

RESUMO

Nuestro objetivo es proporcionar al clínico los conocimientos básicos para la interpretación de datos referidos a enfermedades genéticas que le sirvan de ayuda a la hora de tomar decisiones clínicas. Se hace un símil del genoma humano con una enciclopedia, la «enciclopedia de la vida», analizando como se transmite la información genética, las causas, las consecuencias y las principales reglas de nomenclatura de las mutaciones. Se discute a continuación qué mutaciones y cómo pueden contribuir a la aparición de la enfermedad cardiovascular. Por último, se describe la contribución de la genética a la mejora del diagnóstico y el tratamiento de la hipercolesterolemia familiar (HF), una de las entidades en que el tratamiento hipolipemiante es eficaz y coste-efectivo. Se justifica el empleo de técnicas de detección genética a gran escala como son los biochips que analizan las principales mutaciones de los genes que originan el HF (AU)


The main aim of this article is to provide clinicians with the basic knowledge needed to interpret data on genetic disorders that may be relevant to clinical decision-making. The human genome is likened to an encyclopedia, «The encyclopedia of life», which is used to explain how genetic information is transmitted and to describe the causes and consequences of mutations, along with the main rules used for naming them. There follows a discussion of which mutations can contribute to the development of cardiovascular disease and how they do so. Finally, there is a description of how genetics has contributed to improvements in the diagnosis and treatment of familial hypercholesterolemia, one of the conditions in which lipid-lowering therapy is efficacious and cost-effective. In addition, there is an explanation of how large-scale genetic assays, such as biochips, are used for detecting the principle mutations found in the genes responsible for familial hypercholesterolemia (AU)


Assuntos
Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Hiperlipoproteinemia Tipo II/genética , Mutagênese , Mutagênese/genética , Transcrição Gênica/genética , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/diagnóstico
12.
Dentum (Barc.) ; 7(3): 124-130, jul.-sept. 2007. ilus
Artigo em Es | IBECS | ID: ibc-65796

RESUMO

Las perspectivas creadas por las técnicas de regeneración tisular en odontología son muy importantes. Los mecanismos moleculares de la morfogénesis dental están siendo descritos en relación con sus factores causales, tanto genéticos como epigenéticos. El conocimiento de estos factores permitirá a medio plazo influir en los mecanismos biomoleculares del crecimiento y el desarrollo, no sólo oral sino general. El presente trabajo revisa las publicaciones más recientes dedicadas a la regeneración dental, cuyos resultados, aunque esperanzadores, todavía distan de poder aplicarse clínicamente en nuestras consultas (AU)


The prospects for tooth regeneration in dentistry are promising. The molecular mechanisms of the dental morphogenesis are being described in relation to its causal factors, genetic as well as epigenetic. Knowledge of those factors will allow in the mid term to influence in the biomolecular mechanisms of the growth and the development, not only oral but general. The present work reviews the most recent publications dedicated to the dental regeneration, whose results, although hopeful, are still far of being able to be applied clinically in our offices (AU)


Assuntos
Regeneração/fisiologia , Regeneração Tecidual Guiada/instrumentação , Regeneração Tecidual Guiada , Morfogênese/genética , Morfogênese/fisiologia , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Implantes Dentários/tendências , Implantes Dentários , Modelos Dentários , Preservação de Tecido , Fatores de Transcrição , Transcrição Gênica
13.
Clin. transl. oncol. (Print) ; 9(8): 521-530, ago. 2007. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-123349

RESUMO

BACKGROUND: Enhanced removal of cisplatin-DNA adducts has been reported as one of main causes of cell resistance to cisplatin. This particular resistance mechanism may be circumvented by platinum complexes that bind differently to DNA. One line of work is focussed on trans platinum complexes, some of which exhibit antitumour activity similar to or even higher than that of their cis counterparts. METHODS: We synthesised new trans platinum complexes, trans-[PtCl2(cyclohexylamine)(dimethylamine)] and trans-[PtCl2(OH)2(cyclohexylamine)(dimethylamine)], previously evaluated as cytotoxic agents towards different cancer and normal cell lines. These trans platinum compounds were highly effective against a panel of tumoral cell lines either sensitive to or with acquired resistance to cisplatin. RESULTS: In the present work we examined the mechanisms induced by these compounds to cause tumour cells toxicity. We have found that these compounds induced a complete blockade at the S phase of the cell cycle inhibiting total mRNA transcription and precluding p53 activation. CONCLUSION: In contrast to other DNA-damaging agents, these compounds do not induce senescence-associated permanent arrest. Furthermore, only a small percentage of these cells enter into apoptosis, with most of the population dying by a necrosis-like mechanism (AU)


Assuntos
Humanos , Masculino , Feminino , Antineoplásicos/farmacologia , DNA/biossíntese , Antineoplásicos/síntese química , Compostos Organometálicos/farmacologia , Transcrição Gênica , Antineoplásicos/toxicidade , Apoptose , Senescência Celular , Ciclo Celular , Linhagem Celular Tumoral , Necrose , Compostos Organometálicos/síntese química , Compostos Organometálicos/toxicidade , RNA Mensageiro/metabolismo , Ligantes
14.
J. physiol. biochem ; 63(2): 161-170, abr.-jun. 2007. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-76673

RESUMO

In order to observe the effects of nicotine on protein expression in rat vascularsmooth muscle cells (SMCs), nicotine treated SMCs were studied by proteomic technologiescombining two-dimensional electrophoresis (2-DE) and peptide mass fingerprinting(PMF). Real-time RT–PCR was used to validate the differentiallyexpressed proteins. We found that 11 protein spots were significantly up-regulatedand one down-regulated by nicotine treatment. The results of PMF showed thatthese up- and down-regulated proteins could be divided into three groups accordingto their functions: cytoskeleton proteins, regulatory proteins and enzymes. Simultaneously,we also verified their consistent alteration at the transcriptional levelthrough real-time RT–PCR. The affected proteins turned out to be mainly associatedwith cell migration, proliferation and energy metabolism, and are responsible fornicotine-related cardiovascular damage (AU)


No disponible


Assuntos
Animais , Masculino , Ratos , Músculo Liso Vascular , Nicotina/farmacologia , Proteínas/metabolismo , Proteoma/análise , Proteômica/métodos , Células Cultivadas , Eletroforese em Gel Bidimensional , Imuno-Histoquímica , Espectrometria de Massas , Mapeamento de Peptídeos , Proteínas/genética , Ratos Wistar , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Tripsina/farmacologia
17.
An. R. Acad. Farm ; 73(1): 125-140, ene. 2007. ilus
Artigo em Es | IBECS | ID: ibc-055344

RESUMO

El premio Nobel de Química, en su edición de 2006, ha sido otorgado al Profesor Roger Kornberg, del Departamento de Biología Estructural de la californiana Universidad de Stanford. El Profesor Kornberg ha desarrollado durante años un exhaustivo y riguroso trabajo sobre el complejo de proteínas responsable de la síntesis del ARN mensajero en las células eucarióticas, la RNA polimerasa II. Aplicando metodologías biofísicas, en particular la cristalografía de rayos-X, su trabajo muestra cómo diez de las doce subunidades proteicas del enzima se coordinan para separar las dos hebras de la molécula de ADN, reconocer el primer ribonucleótido que debe incorporarse sobre el molde de la cadena que ha de ser transcrita y catalizar la polimerización de sucesivos nucleótidos con gran fidelidad y procesividad. Cerca de medio siglo después de que Severo Ochoa realizase la primera síntesis bioquímica del ARN en un tubo de ensayo, el trabajo del ahora galardonado desentraña, en sus detalles más íntimos, el funcionamiento de la maquinaria macromolecular esencial para la expresión de los genes


The Nobel Prize in Chemistry 2006 has been awarded to Prof. Roger Kornberg, Head of the Department of Structural Biology, Stanford CA, USA. Prof. Kornberg has been leading along years an exhaustive and rigorous research effort on RNApol II, the protein complex responsible for the synthesis of messenger RNA in eukaryotic cells. By means of biophysical approaches, X-ray crystallography in particular, his work shows how ten of the twelve protein subunits of the whole enzyme are coordinated in order to melt the two DNA strands, recognize the first ribonucleotide to be incorporated on the template chain to be transcribed and catalyze polymerization of successive nucleotide building blocks with astonishing fidelity and processivity. Nearly half a century after the pioneering in vitro synthesis of RNA by Severo Ochoa, the work now awarded unveils, with a wealth of intimate details, the function of the macromolecular machinery essential for gene expression


Assuntos
Humanos , RNA Polimerase II/genética , RNA Polimerase II/biossíntese , Prêmio Nobel , Cristalografia por Raios X/métodos , Transcrição Gênica/genética
18.
Clin. transl. oncol. (Print) ; 8(11): 780-787, nov. 2006. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-126233

RESUMO

Gene expression is mostly controlled at the level of the transcription initiation. The transcription control regions of protein-encoding genes include: the core promoter, where RNA polymerase II binds, the proximal and distal promoter, responsible for gene expression regulation, and the enhancers and silencers. Chromatin represents an additional level of regulation of gene expression. The switching between inactive and active chromatin is closely related to the activity of histone-modifying enzymes and chromatin-remodelling complexes. Transcriptional activation of a gene requires the binding of specific transcription factors to regulatory DNA elements, the opening of the chromatin, the binding of Mediator, and the assembly of the preinitiation complex with RNA polymerase and RNA synthesis initiation. Transcription factors ultimately transduce the proliferation signals elicited by growth factors. Moreover, many human oncogenes encode for transcription factors, and some of them are prevalent in particular neoplasias (e.g., MYC, MLL, PML-RARa). Also, some of the most prominent tumor suppressors (e.g. p53) are transcription factors (AU)


Assuntos
Humanos , Animais , Transformação Celular Neoplásica/genética , Cromatina/genética , Cromatina/ultraestrutura , Metilação de DNA , Elementos Facilitadores Genéticos/genética , Oncogenes , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Fatores de Transcrição/fisiologia , Transcrição Gênica
19.
An. R. Acad. Farm ; 72(4): 563-581, oct. 2006. ilus, tab
Artigo em En | IBECS | ID: ibc-051852

RESUMO

La estabilidad del ARN mensajero está surgiendo como instrumento celular fundamental y efectivo para regular la expresión génica a nivel post-transcripcional. La estabilidad del ARNm se controla vía interacciones coordinadas entre componentes estructurales del ARNm (elementos cis) y factores trans específicos. Los determinantes de estabilidad de ARNm más conocidos y eficientes son los elementos ricos en adenina y uridina (ARE) que, a través de su unión con proteínas de unión a ARE (AUBPS), modulan la estabilidad de los transcritos y/o su traducción. Alteraciones en cualquiera de estos componentes puede dar lugar a enfermedades. Aquí revisamos las alteraciones genéticas en elementos regulatorios del 3’UTR, así como las aberraciones en los niveles, localización subcelular y modificaciones posttraslacionales de AUBPs que están asociadas a enfermedades humanas. Un conocimiento detallado de estas alteraciones y su impacto en la regulación de la estabilidad del ARNm revelará nuevas dianas para su aplicación terapéutica


mRNA stability is emerging as a fundamental and effective cellular tool to regulate gene expression at posttranscriptional levels. mRNA stability is controlled via orchestrated interactions between mRNA structural components (cis-elements) and specific trans-acting factors. The most widespread and efficient determinant of RNA stability are the adenylate and uridylate-rich elements (ARE) that, through binding of ARE-binding proteins (AUBPs), modulate the stability of transcripts and/or their translation. Alterations in any of these components can lead to disease. Here, we review the genetic alterations in 3’UTR regulatory sequences as well as the aberrant levels, subcellular localization, and posttranslational modifications of AUBPs that are linked to human diseases. A thorough understanding of these alterations and their impact on mRNA stability regulation will uncover promising new targets for therapeutic intervention


Assuntos
Humanos , Regulação da Expressão Gênica , Estabilidade de RNA/genética , RNA Mensageiro/genética , Doença de Alzheimer/genética , Inflamação/genética , Talassemia/genética , Neoplasias/genética , Transcrição Gênica , Uridina/genética , Adenina , Ligação Proteica/genética
20.
An. R. Acad. Farm ; 72(4): 611-627, oct. 2006. ilus, tab
Artigo em En | IBECS | ID: ibc-051855

RESUMO

Four distinct eukaryotic initiation factor 2á (eIF2á) kinases phosphorylate eIF2á at Ser-51 and regulate protein synthesis in response to cellular stress conditions. This kinase family includes the hemin-regulated inhibitor (HRI); the doublestranded RNA-dependent kinase (PKR); the GCN2 protein kinase; and the endoplasmic reticulum-resident kinase (PERK). HRI mediates protein synthesis inhibition in heme-deficient reticulocyte lysates. Although HRI contains two putative heme regulatory motifs (HRMs) that are not present in other eIF2á kinases, the significance of these motifs in heme regulation is not clear. In fact, it had been characterized two novel eIF2á kinases from Schizosaccharomyces pombe that lacked any of the HRMs, but were sensitive to heme regulation in vitro. To investigate the importance of different regions in the regulation of HRI by heme, specific HRI mutants were generated, and kinase activities and heme responsiveness were analyzed in vitro. Mutational analysis indicated that the heme regulatory motifs were spread around some regions in the HRI catalytic domain, outside of the HRMs. In accordance with these results, both the autokinase and the eIF2á kinase activities of three distinct eIF2á kinases, including the human PKR, the mouse GCN2 and the Drosophila PERK were inhibited in vitro by hemin. Although the known regulatory mechanisms of these eIF2á kinases are very different, the data reported here indicate that all known eIF2á kinases are regulated in vitro by hemin. This finding provides evidence that hemin represents a regulatory mechanism unique to eIF2á kinases and underscores the role of hemin in the translational regulation of eukaryotic cells


Las cuatro eIF2á quinasas eucarióticas fosforilan el residuo Ser-51 de la subunidad alfa del factor de iniciación 2 y regulan la síntesis de proteínas en respuesta a situaciones de estrés celular. Esta familia de proteínas quinasas está formada por el inhibidor regulado por hemina (HRI); la quinasa dependiente de RNA de doble cadena (PKR); la proteína quinasa GCN2 y la quinasa residente en el retículo endoplásmico (PERK). El HRI inhibe la síntesis de proteínas en lisados de reticulocitos de conejo deficientes de hemina. Aunque el HRI contiene dos supuestos motivos reguladores de hemina (HRMs), que no están presentes en las otras eIF2á quinasas, no está claro aún el papel de estos motivos en la regulación por hemina. De hecho, se han caracterizado dos nuevas eIF2á quinasas de Schizosaccharomyces pombe que carecen de dichos HRMs, pero son sensibles a la regulación por hemina in vitro. Un análisis mutacional indicó que los motivos reguladores de hemina estaban dispersos a lo largo del dominio catalítico, fuera de los HRMs. De acuerdo con estos resultados, las actividades autoquinasa y eIF2á quinasa de tres eIF2á quinasas distintas, la PKR humana, la GCN2 de ratón y la PERK de Drosophila, se inhibían por hemina in vitro. Aunque los mecanismos de regulación de todas estas eIF2á quinasas son muy diferentes, nuestros resultados indican que todas las eIF2á quinasas se regulan por hemina in vitro. Este descubrimiento soporta la evidencia de que la hemina representa un mecanismo de regulación específico de las eIF2á quinasas, y subraya su papel en la regulación de la traducción de células eucarióticas


Assuntos
Animais , Humanos , eIF-2 Quinase/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fibroblastos/metabolismo , Heme/genética , Heme/metabolismo , Biossíntese de Proteínas/genética , Regulação para Cima , Transcrição Gênica , Células Cultivadas , Fosforilação
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