Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.

Hdl Handle:
http://hdl.handle.net/10147/132278
Title:
Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.
Authors:
Greene, Catherine M; McElvaney, Noel G
Affiliation:
Catherine M Greene, Noel G McElvaney, Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Citation:
Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response. 2010, 1 (5):94-101 World J Gastrointest Pharmacol Ther
Journal:
World journal of gastrointestinal pharmacology and therapeutics
Issue Date:
6-Oct-2010
URI:
http://hdl.handle.net/10147/132278
DOI:
10.4292/wjgpt.v1.i5.94
PubMed ID:
21577302
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091154/pdf/WJGPT-1-94.pdf
Abstract:
The serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.
Item Type:
Article
Language:
en
ISSN:
2150-5349

Full metadata record

DC FieldValue Language
dc.contributor.authorGreene, Catherine Men
dc.contributor.authorMcElvaney, Noel Gen
dc.date.accessioned2011-05-27T15:27:48Z-
dc.date.available2011-05-27T15:27:48Z-
dc.date.issued2010-10-06-
dc.identifier.citationZ α-1 antitrypsin deficiency and the endoplasmic reticulum stress response. 2010, 1 (5):94-101 World J Gastrointest Pharmacol Theren
dc.identifier.issn2150-5349-
dc.identifier.pmid21577302-
dc.identifier.doi10.4292/wjgpt.v1.i5.94-
dc.identifier.urihttp://hdl.handle.net/10147/132278-
dc.description.abstractThe serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.-
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091154/pdf/WJGPT-1-94.pdfen
dc.titleZ α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.en
dc.typeArticleen
dc.contributor.departmentCatherine M Greene, Noel G McElvaney, Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.en
dc.identifier.journalWorld journal of gastrointestinal pharmacology and therapeuticsen
dc.description.provinceLeinster-

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