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Effect of Aldosterone and Glycyrrhetinic Acid on the Protein Expression of PAI-1 and p22phox in Human Mononuclear Leukocytes
Open accessAbstract
Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 × 10−8m aldosterone (p22phox/β-actin = 1.38 ± 0.05 and PAI-1/β-actin = 1.80 ± 0.05). The same effect was also found with 3 × 10−5m glycyrrhetinic acid, the principal constituent of licorice root (p22phox/β-actin = 1.37 ± 0.97 and PAI-1/β-actin = 1.80 ± 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 × 10−6m of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 × 10−9m aldosterone. Incubations with 1 × 10−9m for 3 hours as well as 1 × 10−8m aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors.
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“subsequent studies confirmed that the incubation of lymphocytes with excess aldosterone increased the protein expression of PAI 1 and p22phox, two markers of inflammation [16].”
From Controversies in the Pathogenesis, Diagnosis and Treatment of PCOS: Focus on Insulin Resistance, Inflammation, and Hyperandrogenism (2022) · cites this paper as [16]
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Batiha, G. E., Beshbishy, A. M., El‐Mleeh, A., Abdel‐Daim, M. M., & Devkota, H. P. (2020) · Biomolecules · doi:10.3390/biom10030352 · Cited by 488
Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis
Brown, N. J. (2013) · Nature Reviews Nephrology · doi:10.1038/nrneph.2013.110 · Cited by 464
Armanini, D., Boscaro, M., Bordin, L., & Sabbadin, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084110 · Cited by 324
Self-citationAldosterone and end-organ damage
Brown, N. J. (2005) · Current Opinion in Nephrology & Hypertension · doi:10.1097/01.mnh.0000165889.60254.98 · Cited by 321
Rickard, A. J., Morgan, J., Tesch, G. H., Funder, J. W., Fuller, P. J., & Young, M. J. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.131110 · Cited by 315
Metadata
- Authors
- Calò, L. A., Zaghetto, F., Pagnin, E., Davis, P. A., de Mozzi, P., Sartorato, P., Martire, G., Fiore, C., & Armanini, D.
- Affiliations
- Department of Clinical and Experimental Medicine, Clinica Medica 4 (L.A.C., F.Z., E.P., P.D.M.), University of Padua, Padua 35100, Italy;
- University of Padua (IT)
- University of California, Davis (US)
- Corresponding author
- Armanini, Decio
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-04-01
- Volume
- 89
- Issue
- 4
- Pages
- 1973-1976
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1996601414
- Cited by
- 122
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 2 · 2020: 4 · 2019: 9 · 2018: 9 · 2017: 4 · 2016: 11 · 2015: 1 · 2014: 4 · 2013: 6 · 2012: 4
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacological Effects of Natural Compounds
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- aldosterone, glycyrrhetinic acid, plasminogen activator inhibitor-1, p22phox, mononuclear leukocytes, mineralocorticoid receptor, oxidative stress, hyperaldosteronism, canrenone, licorice, fibrosis
- MeSH terms
- Adult, Aldosterone, Mineralocorticoid Receptor Antagonists, Canrenone, Dose-Response Relationship, Drug, Drug Synergism, Female, Glycyrrhetinic Acid, Humans, Leukocytes, Mononuclear, Male, NADPH Dehydrogenase, Phosphoproteins, Plasminogen Activator Inhibitor 1, NADPH Oxidases, Membrane Transport Proteins
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