Abstract
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.
Highlights
Selenium (Se) is a dietary trace element required for many aspects of human health
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with lung and liver manifestations [2]
SEPS1 is an endoplasmic reticulum (ER) protein involved in the ER stress response and degradation of misfolded proteins, such as ZAAT; its activity depends on a key selenocysteine residue in its active site
Summary
Selenium (Se) is a dietary trace element required for many aspects of human health. Deficiency in selenium is associated with a range of morbidities, such as immunosuppression, viral infections, hypothyroidism and cardiovascular disease among many others. Se is essential due to its requirement by the 21st amino acid, selenocysteine, which is present in selenoproteins [1]. This family of proteins includes glutathione peroxidases, thioredoxin reductases, iodothyronine deiodinases and other selenoproteins such as selenoprotein S (SEPS1). Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with lung and liver manifestations [2]. Misfolded ZAAT is expressed by cells in the lung and may contribute to the pulmonary inflammatory manifestations of the disorder. Little is known regarding the specific factors that predispose ZAATD individuals to lung or liver disease environmental or idiosyncratic differences at the genetic level are likely to contribute. SEPS1 is an ER protein involved in the ER stress response and degradation of misfolded proteins, such as ZAAT; its activity depends on a key selenocysteine residue in its active site
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
