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Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils

Alba, G., El Bekay, R., Chacon Fernandez, Pedro, Reyes, M. E., Ramos, E., Olivan, J., Jimenez, J., Lopez, J. M., Martin-Nieto, J., Pintado, E. and Sobrino, F. 2008. Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils. Journal of leukocyte biology 84 (2) , pp. 397-405. 10.1189/jlb.0108035

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Angiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Δ12,14-PGJ2 (15dPGJ2). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ2-dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ2 on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ2-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Society for Leukocyte Biology
ISSN: 0741-5400
Last Modified: 28 Jun 2019 02:02

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