Is There a Therapeutic Role for Selenium in Alpha-1 Antitrypsin Deficiency?
Open accessAbstract
Selenium is an essential trace mineral of fundamental importance to human health. Much of its beneficial influence is attributed to its presence within selenoproteins, a group of proteins containing the rare amino acid selenocysteine. There are 25 known human selenoproteins including glutathione peroxidases, thioredoxin reductases and selenoproteins. Selenoprotein S (SEPS1) is an endoplasmic reticulum (ER) resident selenoprotein involved in the removal of misfolded proteins from the ER. SEPS1 expression can be induced by ER stress, an event that is associated with conformational disorders and occurs due to accumulation of misfolded proteins within the ER. Alpha-1 antitrypsin (AAT) deficiency, also known as genetic emphysema, is a conformational disorder in which the roles of ER stress, SEPS1 and selenium have been investigated. SEPS1 can relieve ER stress in an in vitro model of AAT deficiency by reducing levels of active ATF6 and inhibiting grp78 promoter- and NFκB activity; some of these effects are enhanced in the presence of selenium supplementation. Other studies examining the molecular mechanisms by which selenium mediates its anti-inflammatory effects have identified a role for prostaglandin 15d-PGJ2 in targeting NFκB and PPARγ. Together these ER stress-relieving and anti-inflammatory properties suggest a therapeutic potential for selenium supplementation in genetic emphysema.
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Selenium supplementation enhances the synthesis of electrophilic cyclopentenone 15d-PGJ2, a potent Nrf2 agonist, significantly increasing the cellular antioxidant pool and anti-inflammatory properties.
“Selenium supplementation enhances the synthesis of electrophilic cyclopentenone 15d-PGJ2, a very potent Nrf2 agonist, significantly increasing the cellular antioxidant pool and anti-inflammatory properties (Greene et al. 2013).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Greene et al. 2013
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- Authors
- Greene, C., Chhabra, R., & McElvaney, N.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Corresponding author
- Greene, Catherine
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2013-03-11
- Volume
- 5
- Issue
- 3
- Pages
- 758-770
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC3705318
- OpenAlex
- W1970180488
- Cited by
- 4
- References
- 67
- Citations by year
- 2023: 1 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion, cc-by-nc-sa)
- Funders
- Medical Research Charities Group
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Organoselenium and organotellurium chemistry
- Keywords
- selenium supplementation, alpha-1 antitrypsin deficiency, selenoproteins, selenoprotein S, endoplasmic reticulum stress, ATF6, GRP78, NF-κB, PPARγ, anti-inflammatory activity, selenocysteine
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Humans, Membrane Proteins, Selenium, alpha 1-Antitrypsin Deficiency, Genetic Predisposition to Disease, Selenoproteins
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