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.

Poor and under pressure: the social impact of Europe's fiscal consolidation. Bruegel Policy Contribution, Issue 2015/04, March 2015

Europe faces major challenges related to poverty, unemployment and polarisation between the south and the north, which impact adversely the current living conditions of many citizens, and also negatively impact medium- and long-term economic growth. Fiscal consolidation exaggerated social hardship. In vulnerable countries there was no alternative to fiscal consolidation, but in most EU countries and at aggregate EU level, consolidation was premature when the cyclical position of the economy was deteriorating. Spending on social protection was shielded relative to other spending categories, but public bank rescue costs were high. While the changes in the tax mix favoured job creation, the overall tax burden become more regressive. There is an increasing generational divide between the elderly and the young in terms of social indicators. Social spending on elderly people was favoured relative to spending on families, children and education. There is now a serious danger that a lost generation might develop in several member states. Forceful policies should include bold structural reforms, better use of the European economic governance framework, more demand promotion, and a revision of national tax/benefit systems for fair burden sharing between the wealthy and poor.

Waste and financial management problems at the Air Force : hearing before the Committee on Governmental Affairs, United States Senate, One Hundred Second Congress, second session, February 19, 1992.

Shipping list no.: 92-0609-P.

Manual of surgical anatomy : authorized by the Secretary of War and under the supervision of the Surgeon General and Council of National Defense /

Includes explanatory index.

The book of household management : comprising information for the mistress, housekeeper, cook, kitchen-maid, butler, footman, coachman, valet, upper and under house maids, lady's-maid, maid-of-all-work, laundry-maid, nurse and nurse-maid, monthly, wet, and sick nurses, etc. etc. : also, sanitary, medical, and legal memoranda : with a history of the origin, properties, and uses of all things connected with home life and comfort /

Includes index.

Investigations of basic geometric quality of aerial photographs and some related problems /

"17 August 1962."

A treatise on the law arising before justices of the peace and in business transactions : as administered in courts of record in Ohio, and under the Revised Statutes of 1880 : with practical forms /

Includes index.