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1.
Int Rev Cell Mol Biol ; 374: 37-81, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36858656

RESUMO

Legionella pneumophila is the causative agent of Legionnaires' disease, a severe pneumonia. L. pneumophila injects via a type-IV-secretion-system (T4SS) more than 300 bacterial proteins into macrophages, its main host cell in humans. Certain of these bacterial effectors target organelles in the infected cell and hijack multiple processes to facilitate all steps of the intracellular life cycle of this pathogen. In this review, we discuss the interplay between L. pneumophila, an intracellular bacterium fully armed with virulence tools, and mitochondria, the extraordinary eukaryotic organelles playing prominent roles in cellular bioenergetics, cell-autonomous immunity and cell death. We present and discuss key findings concerning the multiple interactions of L. pneumophila with mitochondria during infection and the mechanisms employed by T4SS effectors that target mitochondrial functions to subvert infected cells.


Assuntos
Legionella , Humanos , Mitocôndrias , Morte Celular , Eucariotos , Macrófagos
2.
Dis Model Mech ; 11(6)2018 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-29752286

RESUMO

Cisplatin and derivatives are commonly used as chemotherapeutic agents. Although the cytotoxic action of cisplatin on cancer cells is very efficient, clinical oncologists need to deal with two major difficulties, namely the onset of resistance to the drug and the cytotoxic effect in patients. Here, we used Caenorhabditis elegans to investigate factors influencing the response to cisplatin in multicellular organisms. In this hermaphroditic model organism, we observed that sperm failure is a major cause of cisplatin-induced infertility. RNA sequencing data indicate that cisplatin triggers a systemic stress response, in which DAF-16/FOXO and SKN-1/NRF2, two conserved transcription factors, are key regulators. We determined that inhibition of the DNA damage-induced apoptotic pathway does not confer cisplatin protection to the animal. However, mutants for the pro-apoptotic BH3-only gene ced-13 are sensitive to cisplatin, suggesting a protective role of the intrinsic apoptotic pathway. Finally, we demonstrated that our system can also be used to identify mutations providing resistance to cisplatin and therefore potential biomarkers of innate cisplatin-refractory patients. We show that mutants for the redox regulator trxr-1, ortholog of the mammalian thioredoxin reductase 1 TRXR1, display cisplatin resistance. By CRISPR/Cas9, we determined that such resistance relies on the presence of the single selenocysteine residue in TRXR-1.This article has an associated First Person interview with the first author of the paper.


Assuntos
Antineoplásicos/farmacologia , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Cisplatino/farmacologia , Animais , Apoptose/efeitos dos fármacos , Bioensaio , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Masculino , Mutação de Sentido Incorreto/genética , Análise de Sequência de RNA , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Transcrição Gênica/efeitos dos fármacos
3.
Rev. biol. trop ; 59(3): 1115-1126, Sept. 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-638146

RESUMO

In Mexico and elsewhere in the Caribbean, the queen conch Strombus gigas is an endangered species. Understanding the genetic connectivity of their populations will support management strategies for long term conservation of the species. Genetic diversity and population differentiation was assessed from samples collected at Banco Chinchorro and Isla Cozumel in the Mexican Caribbean and at Arrecife Alacranes in the Gulf of Mexico. Samples were obtained from the commercial capture at Banco Chinchorro (n=50) and Isla Cozumel (n=40) on March 2004. On November 2004, a non-invasive method for the Arrecife Alacranes sampling was applied, taking the hemolymph of live animals (n=65) and releasing them to the wild. The mitochondrial DNA variation at two genes (COI and Cyt-b) was analyzed. Genetic diversity at the three locations ranged between 0.55-0.65 in COI and 0.87-0.94 in Cyt-b, showing no bottleneck evidences. A non-significant fixation index (F ST=0.019, p=0.161) and a Maximum Parsimony Network tree that did not show particular clades associated with any of the geographical locations, suggested a lack of statistically significant genetic differentiation among populations. Nevertheless, the cline patterns observed in both genetic diversity and haplotypic frequencies from Banco Chinchorro through Arrecife Alacranes, and the larger genetic distance between these locations from those between Isla Cozumel, Banco Chinchorro and Arrecife Alacranes, suggest the possibility of a pattern of isolation-by distance. The role of the main current systems over the potential genetic differences in S. gigas populations along the Mexican Caribbean, and the conservation management of S. gigas at these locations as discrete units is discussed. Rev. Biol. Trop. 59 (3): 1115-1126. Epub 2011 September 01.


El caracol rosado Strombus gigas es una especie amenzada en México y otros sitios del Caribe. Su conservación a largo plazo requiere la comprensión de la conectividad entre sus poblaciones. En este estudio se evaluó la diversidad y diferenciación genética de muestras recolectadas en tres sitios del Caribe y Golfo de México adyacentes a la Península de Yucatán. Las muestras se obtuvieron de la captura comercial en Banco Chinchorro (n=50) e Isla Cozumel (n=40) en marzo de 2004. En noviembre de 2004 se obtuvieron muestras de Arrecife Alacranes (n=65) de animales vivos, mediante un método no invasivo diseñado para la obtención de hemolinfa; los organismos muestreados se liberaron de vuelta al medio natural. Se analizó la diversidad genética de dos genes del ADN mitocondrial (COI y Cyt-b). La diversidad genética en las tres localidades varió entre 0.55 - 0.65 en COI y 0.87 - 0.94 en Cyt-b no indicando reducción por cuello de botella. Un índice de fijación no significativamente diferente de cero (F ST=0.019, p=0.161) y un árbol en Red de Máxima Parsimonia que no mostró clados particulares asociados con localidades específicas, sugiere que no hay diferencias genéticas significativas entre sitios. Sin embargo, los patrones clinales observados en la diversidad genética y en las frecuencias haplotípicas, así como la mayor distancia genética registrada entre las localidades más alejadas (Banco Chinchorro y Arrecife Alacranes) sugiere un posible un patrón de aislamiento por distancia. Se discute el papel de los sistemas de corrientes principales del Caribe mexicano sobre la posible diferenciación genética de S. gigas. Asimismo, se discute el manejo de las localidades estudiadas como unidades discretas.


Assuntos
Animais , Espécies em Perigo de Extinção , Variação Genética , Caramujos/classificação , Caramujos/genética , DNA Mitocondrial/genética , Geografia , Haplótipos , México , Dinâmica Populacional
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