Histone acetyltransferases derived RW20 protects and promotes rapid clearance of Pseudomonas aeruginosa in zebrafish larvae / La histona acetiltransferasa derivada RW20 protege y promueve la rápida eliminación de Pseudomonas aeruginosa en larvas de pez cebra

Pseudomonas is a group of bacteria that can cause a wide range of infections, particularly in people with weakened immune systems, such as those with cystic fibrosis or who are hospitalized. It can also cause infections in the skin and soft tissue, including cellulitis, abscesses and wound infections. Antimicrobial peptides (AMPS) are the alternative strategy due to their broad spectrum of activity and act as effective treatment against multi-drug resistance pathogens. In this study, we have used an AMP, RW20 (1RPVKRKKGWPKGVKRGPPKW20). RW20 peptide is derived from the histone acetyltransferases (HATs) of the freshwater teleost, Channa striatus. The antimicrobial prediction tool has been utilized to identify the RW20 sequence from the HATs sequence. We synthesized the peptide to explore its mechanism of action. In an in vitro assay, RW20 was challenged against P. aeruginosa and we showed that RW20 displayed antibacterial properties and damaged the cell membrane. The mechanism of action of RW20 against P. aeruginosa has been established via field emission scanning electron microscopy (FESEM) as well as fluorescence assisted cell sorter (FACS) analysis. Both these experiments established that RW20 caused bacterial membrane disruption and cell death. Moreover, the impact of RW20, in-vivo, was tested against P. aeruginosa-infected zebrafish larvae. In the infected larvae, RW20 showed protective effect against P. aeruginosa by increasing the larval antioxidant enzymes, reducing the excess oxidative stress and apoptosis. Thus, it is possible that HATs-derived RW20 can be an efficient antimicrobial molecule against P. aeruginosa.(AU)

Síntesis y evaluación de nuevos inhibidores de las HDAC / Synthesis and evaluation of new HDAC inhibitors

La acetilación de residuos de lisina en las histonas está mediada por las enzimas denominadas histona acetiltransferasas (HAT). Los grupos acetilo son eliminados de las e-N-acetil-lisinas por la actividadde las histonas desacetilasas (HDAC). El balance entre las actividades opuestas de las HAT y las HDAC regula el estado de acetilación de las histonas. Este tipo de modificaciones regulan en la célula procesos fundamentales clave en respuesta a señales extracelulares. En general, altos niveles de acetilación (hiperacetilación) se asocian a un incremento de la actividad transcripcional, mientras que bajos niveles de acetilación (hipoacetilación) se asocian a la represión de la expresión genética. Actualmente se conocen diversos tipos de inhibidores de las HDAC que pueden reactivar la expresión genética e inhibir el crecimiento de las células tumorales, por lo que se investiga su uso en el tratamiento frente al cáncer. Sería deseable identificar nuevos inhibidores de las enzimas HDAC para su utilización en el tratamiento o profilaxis de enfermedades en las que la inhibición de dichas enzimas HDAC está implicada. Se han obtenido 10 nuevos inhibidores de las HDAC y se ha evaluado su actividad frente a HDAC aislada. Se discute la importancia de las modificaciones realizadas en el espaciador(AU)

Lysine residues acetylation on histones is mediated by histone acetyltransferase (HAT). The acetyl groups are removed from e-N-acetyl-lysine by the histone deacetylase (HDAC) activity. The balance between the HATs and HDACs activities regulates the histone acetylation status. Such changes regulate key processes in the cell in response to extracellular signals. Mostly, high levels of acetylation(hyperacetylation) are associated with increased transcriptional activity. Low levels of acetylation (hypoacetylation) are associated with repression of gene expression. Currently, different types of HDAC inhibitors are known to reactivate gene expression and inhibit tumor cell growth. We aim at identifying novel HDAC inhibitors for the treatment or prophylaxis of cancer diseases. Ten new HDAC inhibitors have been obtained and their potency as HDAC inhibitors has been evaluated. A structure-activity relationship discussion has been focused on the structural changes made in the spacer(AU)