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

Hdl Handle:
http://hdl.handle.net/10147/127627
Title:
Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.
Authors:
Kelly, Emer; Greene, Catherine M; Carroll, Tomás P; McElvaney, Noel G; O'Neill, Shane J
Affiliation:
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Citation:
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 chemistry
Issue Date:
19-Jun-2009
URI:
http://hdl.handle.net/10147/127627
DOI:
10.1074/jbc.M109.006288
PubMed ID:
19398551
Additional Links:
http://www.jbc.org/content/284/25/16891.full.pdf+html
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.
Item Type:
Article
Language:
en
MeSH:
Base Sequence; Cell 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
ISSN:
1083-351X

Full metadata record

DC FieldValue Language
dc.contributor.authorKelly, Emeren
dc.contributor.authorGreene, Catherine Men
dc.contributor.authorCarroll, Tomás Pen
dc.contributor.authorMcElvaney, Noel Gen
dc.contributor.authorO'Neill, Shane Jen
dc.date.accessioned2011-04-07T08:20:49Z-
dc.date.available2011-04-07T08:20:49Z-
dc.date.issued2009-06-19-
dc.identifier.citationSelenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency. 2009, 284 (25):16891-7 J. Biol. Chem.en
dc.identifier.issn1083-351X-
dc.identifier.pmid19398551-
dc.identifier.doi10.1074/jbc.M109.006288-
dc.identifier.urihttp://hdl.handle.net/10147/127627-
dc.description.abstractZ 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.-
dc.language.isoenen
dc.relation.urlhttp://www.jbc.org/content/284/25/16891.full.pdf+htmlen
dc.subject.meshBase Sequence-
dc.subject.meshCell Line-
dc.subject.meshDNA Primers-
dc.subject.meshEndoplasmic Reticulum-
dc.subject.meshGene Expression-
dc.subject.meshGenetic Variation-
dc.subject.meshGlutathione Peroxidase-
dc.subject.meshHeat-Shock Proteins-
dc.subject.meshHumans-
dc.subject.meshMembrane Proteins-
dc.subject.meshNF-kappa B-
dc.subject.meshPromoter Regions, Genetic-
dc.subject.meshRecombinant Proteins-
dc.subject.meshSelenium-
dc.subject.meshSelenoproteins-
dc.subject.meshStress, Physiological-
dc.subject.meshTransfection-
dc.subject.meshalpha 1-Antitrypsin-
dc.subject.meshalpha 1-Antitrypsin Deficiency-
dc.titleSelenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.en
dc.typeArticleen
dc.contributor.departmentRespiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.en
dc.identifier.journalThe Journal of biological chemistryen
dc.description.provinceLeinster-

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