Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.
Affiliation
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.Issue Date
2009-06-19MeSH
Base SequenceCell Line
DNA Primers
Endoplasmic Reticulum
Gene Expression
Genetic Variation
Glutathione Peroxidase
Heat-Shock Proteins
Humans
Membrane Proteins
NF-kappa B
Promoter Regions, Genetic
Recombinant Proteins
Selenium
Selenoproteins
Stress, Physiological
Transfection
alpha 1-Antitrypsin
alpha 1-Antitrypsin Deficiency
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Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency. 2009, 284 (25):16891-7 J. Biol. Chem.Journal
The Journal of biological chemistryDOI
10.1074/jbc.M109.006288PubMed ID
19398551Additional Links
http://www.jbc.org/content/284/25/16891.full.pdf+htmlAbstract
Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.Item Type
ArticleLanguage
enISSN
1083-351Xae974a485f413a2113503eed53cd6c53
10.1074/jbc.M109.006288
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