Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.125
Filtrar
3.
Nat Struct Mol Biol ; 26(9): 766-770, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439939

RESUMO

The discovery of RNA polymerases I, II, and III opened up a new era in gene expression. Here I provide a personal retrospective account of the transformation of the DNA template, as it evolved from naked DNA to chromatin, in the biochemical analysis of transcription by RNA polymerase II. These studies have revealed new insights into the mechanisms by which transcription factors function with chromatin to regulate gene expression.


Assuntos
Bioquímica/história , DNA/metabolismo , Biologia Molecular/história , RNA Polimerase II/metabolismo , RNA Mensageiro/biossíntese , Transcrição Genética , História do Século XX , História do Século XXI
4.
Nat Struct Mol Biol ; 26(9): 771-776, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439940

RESUMO

The discovery of the three eukaryotic nuclear RNA polymerases paved the way for serious biochemical investigations of eukaryotic transcription and the identification of eukaryotic transcription factors. Here we describe this adventure from our vantage point, with a focus on the hunt for factors that regulate elongation by RNA polymerase II.


Assuntos
Bioquímica/história , Eucariotos/enzimologia , Biologia Molecular/história , RNA Polimerase II/metabolismo , Transcrição Genética , Fatores de Elongação da Transcrição/isolamento & purificação , Fatores de Elongação da Transcrição/metabolismo , História do Século XX , História do Século XXI
5.
Nat Struct Mol Biol ; 26(9): 777-782, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439942

RESUMO

Transcription regulation is critical to organism development and homeostasis. Control of expression of the 20,000 genes in human cells requires many hundreds of proteins acting through sophisticated multistep mechanisms. In this Historical Perspective, I highlight the progress that has been made in elucidating eukaryotic transcriptional mechanisms through an array of disciplines and approaches, and how this concerted effort has been driven by the development of new technologies.


Assuntos
Bioquímica/história , Bioquímica/métodos , Eucariotos/enzimologia , Eucariotos/genética , Biologia Molecular/história , Biologia Molecular/métodos , Transcrição Genética , História do Século XX , História do Século XXI
6.
Nat Struct Mol Biol ; 26(9): 783-791, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31439941

RESUMO

The landmark 1969 discovery of nuclear RNA polymerases I, II and III in diverse eukaryotes represented a major turning point in the field that, with subsequent elucidation of the distinct structures and functions of these enzymes, catalyzed an avalanche of further studies. In this Review, written from a personal and historical perspective, I highlight foundational biochemical studies that led to the discovery of an expanding universe of the components of the transcriptional and regulatory machineries, and a parallel complexity in gene-specific mechanisms that continue to be explored to the present day.


Assuntos
Bioquímica/história , Eucariotos/enzimologia , Eucariotos/genética , Biologia Molecular/história , Fatores de Transcrição/isolamento & purificação , Fatores de Transcrição/metabolismo , Transcrição Genética , História do Século XX , História do Século XXI
8.
Nitric Oxide ; 87: 83-89, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30872109

RESUMO

In this review, I provide historical background on how nitric oxide (•NO) and peroxynitrite research was originated in Uruguay in the early 90's and how the investigations evolved through over more than two decades within a context related to human biology. This process involved the participation of multiple local investigators, in conjunction with collaborations at the regional (Latin American) and international levels. The discoveries have been integrated with parallel investigations from other research groups worldwide and, have provided a body of knowledge to unravel how the free radical nitric oxide (•NO) can shift its signal transduction action towards oxidative processes via its interactions with superoxide radical (O2•-) to yield peroxynitrite, a strong biological oxidant. The oxidative biochemistry of peroxynitrite involves both direct reactions and the formation of secondary oxidizing species (i.e. hydroxyl radicals (•OH), carbonate radicals (CO3•-) and nitrogen dioxide (•NO2)) that cause oxidative modifications of biomolecules, including thiol oxidation and tyrosine nitration. Due to the intrinsic instability of peroxynitrite in biological systems, its half-life and fate are largely dictated by its reaction kinetics with biotargets. The direct actions of •NO and peroxynitrite in the modulation of intracellular redox processes are disparate, with peroxynitrite typically causing permanent modifications of cellular components and resulting in severe alterations of cell and mitochondrial homeostasis. Herein, I highlight the evolution and progression of •NO and peroxynitrite research in Uruguay during over 25 years of work, emphasizing hypothesis- and mechanistic-oriented biochemical studies and their translation to medically-relevant conditions.


Assuntos
Bioquímica/história , Pesquisa Biomédica/história , Óxido Nítrico/metabolismo , Ácido Peroxinitroso/metabolismo , Animais , História do Século XX , História do Século XXI , Humanos , Uruguai
9.
Postepy Biochem ; 65(1): 52-57, 2019 Mar 22.
Artigo em Polonês | MEDLINE | ID: mdl-30901183

RESUMO

In 2018 we celebrate the 250th anniversary of the Jedrzej Sniadecki's birth. This work aims to show the importance of his thoughts for the development of natural sciences. He studied at some of the largest universities in Europe, where he met great scientists of the enlightenment. The effects can be seen in his works. He was remembered as a founder of Polish biochemistry, anthropology and pathology, also as the author of chemical terminology and language. The essence of his thoughts is "Theory of Organic being", which is an attempt to answer the question: "what is life?". Jedrzej Sniadecki introduced a new definition of life based on the term "organic power". This work shows how import are the thoughts of Jedrzej Sniadecki in the context of the times in which he lived, as well as the following development of natural sciences, what makes him and his theories worth memory.


Assuntos
Modelos Biológicos , Disciplinas das Ciências Naturais/história , Bioquímica/história , História do Século XVIII , História do Século XIX , Polônia
10.
J Med Biogr ; 27(3): 179-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30848165

RESUMO

Hermann (Hugh) Blaschko was a biochemical pharmacologist best known for discovering how adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine were synthesized, stored, and metabolized in adrenomedullary cells and sympathetic nerves. Blaschko's work not only supported the validity of the concept of neurochemical synaptic transmission but he also made fundamental contributions to the development of drugs used in clinical medicine to treat diseases such as depression, hypertension, and Parkinson's Disease.


Assuntos
Bioquímica/história , Medicina Clínica/história , Farmacologia/história , Catecolaminas/história , Catecolaminas/fisiologia , Inglaterra , Alemanha , História do Século XX , Transmissão Sináptica/fisiologia
12.
J Biol Chem ; 294(6): 1779-1793, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30737317

RESUMO

Omega-6 polyunsaturated fatty acids were identified as essential nutrients in 1930. Their essentiality is largely due to their function as prostaglandin (PG) precursors. I spent most of my career in biochemistry determining how PG biosynthesis is regulated. PGs are lipid mediators formed in response to certain circulating hormones and cytokines. PGs act near their sites of synthesis to signal neighboring cells to coordinate their responses (e.g. when platelets interact with blood vessels). The committed step in PG synthesis is the conversion of a 20-carbon omega-6 fatty acid called arachidonic acid to prostaglandin endoperoxide H2 (PGH2). Depending on the tissue and the hormone or cytokine stimulus, this reaction is catalyzed by either cyclooxygenase-1 or cyclooxygenase-2 (COX-1 or COX-2). Once formed, PGH2 is converted, again depending on the context, to one of several downstream PG subtypes that act via specific G protein-coupled receptors. Nonsteroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen, and naproxen) block PG synthesis by inhibiting COX-1 and COX-2. COX-2 is also inhibited by COX-2-selective inhibitors. Inhibition of COX-1 by low-dose aspirin prevents thrombosis. COX-2 inhibition reduces inflammation and pain. Investigating the mysteries of COXs anchored my scientific career. I attribute my successes to the great good fortune of having been surrounded by people who helped me make the most of my talents. I have written this reflection in a light-hearted fashion as a self-help essay, while highlighting the people and factors that most impacted me during my upbringing and then during my maturation and evolution as a biochemist.


Assuntos
Anti-Inflamatórios não Esteroides , Bioquímica/história , Ciclo-Oxigenase 1 , Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2 , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/história , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/história , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/história , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/história , Inibidores de Ciclo-Oxigenase 2/farmacologia , História do Século XX , História do Século XXI , Humanos , Prostaglandina H2/história , Prostaglandina H2/metabolismo
15.
J Biol Chem ; 294(5): 1638-1642, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710011

RESUMO

Herb Tabor was the Editor-in-Chief of the Journal of Biological Chemistry (JBC) spanning the years 1971-2010. This year, Herb turns 100. What do you give a person turning 100? Our answer to this question was to dedicate two of our favorite JBC papers to Herb. Both of these papers focus on reversible phosphorylation, which we briefly review. In addition, we delve into a new finding that centers around a novel family of secreted kinases, suggesting that there are many new and exciting discoveries yet to explore.


Assuntos
Bioquímica/história , Publicações Periódicas como Assunto , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Quinases/metabolismo , História do Século XX , História do Século XXI , Humanos , Fosforilação
16.
J Biol Chem ; 294(5): 1652-1660, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710013

RESUMO

During Herbert Tabor's tenure as Editor-in-Chief from 1971 to 2010, JBC has published many seminal papers in the fields of chromatin structure, epigenetics, and regulation of transcription in eukaryotes. As of this writing, more than 21,000 studies on gene transcription at the molecular level have been published in JBC since 1971. This brief review will attempt to highlight some of these ground-breaking discoveries and show how early studies published in JBC have influenced current research. Papers published in the Journal have reported the initial discovery of multiple forms of RNA polymerase in eukaryotes, identification and purification of essential components of the transcription machinery, and identification and mechanistic characterization of various transcriptional activators and repressors and include studies on chromatin structure and post-translational modifications of the histone proteins. The large body of literature published in the Journal has inspired current research on how chromatin organization and epigenetics impact regulation of gene expression.


Assuntos
Bioquímica/história , Cromatina/genética , Cromatina/metabolismo , Histonas/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Genética , Epigênese Genética , História do Século XX , História do Século XXI , Humanos , Publicações Periódicas como Assunto , Processamento de Proteína Pós-Traducional
17.
J Biol Chem ; 294(5): 1661-1670, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710014

RESUMO

Throughout the past five decades, tremendous advancements have been made in our understanding of G protein signaling and presynaptic inhibition, many of which were published in the Journal of Biological Chemistry under the tenure of Herb Tabor as Editor-in-Chief. Here, we identify these critical advances, including the formulation of the ternary complex model of G protein-coupled receptor signaling and the discovery of Gßγ as a critical signaling component of the heterotrimeric G protein, along with the nature of presynaptic inhibition and its physiological role. We provide an overview for the discovery and physiological relevance of the two known Gßγ-mediated mechanisms for presynaptic inhibition: first, the action of Gßγ on voltage-gated calcium channels to inhibit calcium influx to the presynaptic active zone and, second, the direct binding of Gßγ to the SNARE complex to displace synaptotagmin downstream of calcium entry, which has been demonstrated to be important in neurons and secretory cells. These two mechanisms act in tandem with each other in a synergistic manner to provide more complete spatiotemporal control over neurotransmitter release.


Assuntos
Bioquímica/história , Publicações Periódicas como Assunto , Terminações Pré-Sinápticas , Receptores Acoplados a Proteínas-G/metabolismo , Transmissão Sináptica , Potenciais de Ação , História do Século XX , História do Século XXI , Humanos
18.
J Biol Chem ; 294(5): 1690-1696, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710015

RESUMO

Hyaluronan has a very simple structure. It is a linear glycosaminoglycan composed of disaccharide units of GlcNAc and d-glucuronic acid with alternating ß-1,4 and ß-1,3 glycosidic bonds that can be repeated 20,000 or more times, a molecular mass >8 million Da, and a length >20 µm. However, it has a very complex biology. It is a major, ubiquitous component of extracellular matrices involved in everything from fertilization, development, inflammations, to cancer. This JBC Review highlights some of these processes that were initiated through publications in the Journal of Biological Chemistry.


Assuntos
Bioquímica/história , Matriz Extracelular/metabolismo , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/metabolismo , Inflamação/fisiopatologia , Cicatrização , História do Século XX , História do Século XXI , Humanos , Publicações Periódicas como Assunto
20.
J Med Biogr ; 27(2): 67-75, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-27885153

RESUMO

Karl Landsteiner applied the sciences of biochemistry, pathology, microbiology, and immunology in medical research to great success during the first half of the 20th century. Although he is principally known for elucidating the major blood group antigens A and B and their isoantibodies for which he was awarded the Nobel Prize in Physiology or Medicine, Landsteiner made many other important medical discoveries. In that respect, he ascertained that paralytic poliomyelitis was due to a virus, the pancreas was damaged in cystic fibrosis, simple chemicals called haptens were able to combine with antibodies, and the Rh antigen that was later found to be the principal cause of hemolytic anemia of the newborn was found in most humans. Moreover, Landsteiner's book "The Specificity of Serological Reactions" was a precursor to the molecular revolution in immunology that occurred after Second World War. Finally, he was one of the leaders of the American Association of Immunology and of the Journal of Immunology.


Assuntos
Alergia e Imunologia/história , Bioquímica/história , Médicos/história , Áustria , Antígenos de Grupos Sanguíneos/história , Europa (Continente) , História do Século XIX , História do Século XX , New York , Sorologia/história
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA