Type

Journal Article

Authors

Shane J O'Neill
Noel G McElvaney
Tomás P Carroll
Catherine M Greene
Emer Kelly

Subjects

Biochemistry

Topics
stress physiological heat shock proteins genetic variation humans metabolism gene expression endoplasmic reticulum recombinant proteins drug therapy genetics selenium blood administration dosage vimp protein human base sequence membrane proteins dna primers alpha 1 antitrypsin nf kappa b transfection alpha 1 antitrypsin deficiency glutathione peroxidase promoter regions genetic molecular chaperone grp78 cell line selenoproteins

Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency. (2009)

Abstract 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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shane J O'Neill, Noel G McElvaney, Tomás P Carroll, Catherine M Greene, Emer Kelly

Experts in our system

1
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 26
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150