Calcineurin expression and activity is regulated by the intracellular redox status and under hypertension in human neutrophils

Calcineurin (protein phosphatase 2B) (CN) comprises a family of serine/threonine phosphatases that play a pivotal role in signal transduction cascades in a variety of cells, including neutrophils. Angiotensin II (Ang II) increases both activity and de novo synthesis of CN in human neutrophils. This study focuses on the role that intracellular redox status plays in the induction of CN activity by Ang II. Both de novo synthesis of CN and activity increase promoted by Ang II were downregulated when cells were treated with l-buthionine-(S,R)-sulfoximine, an inhibitor of synthesis of the antioxidant glutathione. We have also investigated the effect of pyrrolidine dithiocarbamate and phenazine methosulfate, which are antioxidant and oxidant compounds, respectively, and concluded that the intracellular redox status of neutrophils is highly critical for Ang II-induced increase of CN expression and activity. Results obtained in neutrophils from hypertensive patients were very similar to those obtained in these cells on treatment with Ang II. We have also addressed the possible functional implication of CN activation in the development of hypertension. Present findings indicate that downregulation of hemoxygenase-1 expression in neutrophils from hypertensive subjects is likely mediated by CN, which acts by hindering translocation to the nucleus of the transcription factor NRF2. These data support and extend our previous results and those from other authors on modulation of CN expression and activity levels by the intracellular redox status.

Impacto de la mutilación genital femenina en los objetivos del milenio

Objetivo: Relacionar la Mutilación Genital Femenina como factor negativo para la consecución de los Objetivos de Desarrollo del Milenio 1, 3, 4, 5 y 6. Métodos: Se ha realizado la recogida de datos a través de una revisión integradora de la literatura en los años 2014 y 2015. Se consultaron las bases de datos Medline/PubMed, Web of Science, LILACS, SCIELO, Tesis Doctorales TESEO y en las webs de WOK, UNICEF, UNAF y WHO utilizando los descriptores: circuncisión femenina, objetivos de desarrollo del milenio y mutilación genital femenina. Se incluyeron artículos publicados entre los años de 2010 y 2015, y se seleccionaron finalmente 24 artículos. Resultados: La Mutilación Genital Femenina es una práctica basada en discriminaciones de género que refuerza e incentiva el círculo de la pobreza. Provoca complicaciones físicas que pueden repercutir en la mortalidad y morbilidad infantil, así como en complicaciones en el embarazo y el parto y en la adquisición del virus de la inmunodeficiencia humana. Conclusión: La lucha contra la Mutilación Genital Femenina contribuye a la consecución de cinco de los ocho Objetivos del Milenio.