The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.

Hdl Handle:
http://hdl.handle.net/10147/207060
Title:
The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.
Authors:
Greene, Catherine M; Hassan, Tidi; Molloy, Kevin; McElvaney, Noel G
Affiliation:
Respiratory Research Division, Department of Medicine, Royal College of Surgeons , in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. , cmgreene@rcsi.ie
Citation:
Expert Rev Respir Med. 2011 Jun;5(3):395-411.
Journal:
Expert review of respiratory medicine
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207060
DOI:
10.1586/ers.11.20
PubMed ID:
21702661
Abstract:
The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.
Language:
eng
MeSH:
Animals; Endoplasmic Reticulum/*enzymology; Genetic Predisposition to Disease; Heterozygote; Humans; Lung/*enzymology/physiopathology; Lung Diseases/*enzymology/etiology/genetics/physiopathology; Mutation; Peptide Hydrolases/*metabolism; Phenotype; Pulmonary Disease, Chronic Obstructive/enzymology/genetics; Risk Assessment; Risk Factors; Smoking/adverse effects; *Stress, Physiological; alpha 1-Antitrypsin/genetics/*metabolism; alpha 1-Antitrypsin Deficiency/*enzymology/genetics/physiopathology
ISSN:
1747-6356 (Electronic); 1747-6348 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorGreene, Catherine Men_GB
dc.contributor.authorHassan, Tidien_GB
dc.contributor.authorMolloy, Kevinen_GB
dc.contributor.authorMcElvaney, Noel Gen_GB
dc.date.accessioned2012-02-01T09:58:18Z-
dc.date.available2012-02-01T09:58:18Z-
dc.date.issued2012-02-01T09:58:18Z-
dc.identifier.citationExpert Rev Respir Med. 2011 Jun;5(3):395-411.en_GB
dc.identifier.issn1747-6356 (Electronic)en_GB
dc.identifier.issn1747-6348 (Linking)en_GB
dc.identifier.pmid21702661en_GB
dc.identifier.doi10.1586/ers.11.20en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207060-
dc.description.abstractThe serine proteinase inhibitor alpha-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.en_GB
dc.language.isoengen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshEndoplasmic Reticulum/*enzymologyen_GB
dc.subject.meshGenetic Predisposition to Diseaseen_GB
dc.subject.meshHeterozygoteen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLung/*enzymology/physiopathologyen_GB
dc.subject.meshLung Diseases/*enzymology/etiology/genetics/physiopathologyen_GB
dc.subject.meshMutationen_GB
dc.subject.meshPeptide Hydrolases/*metabolismen_GB
dc.subject.meshPhenotypeen_GB
dc.subject.meshPulmonary Disease, Chronic Obstructive/enzymology/geneticsen_GB
dc.subject.meshRisk Assessmenten_GB
dc.subject.meshRisk Factorsen_GB
dc.subject.meshSmoking/adverse effectsen_GB
dc.subject.mesh*Stress, Physiologicalen_GB
dc.subject.meshalpha 1-Antitrypsin/genetics/*metabolismen_GB
dc.subject.meshalpha 1-Antitrypsin Deficiency/*enzymology/genetics/physiopathologyen_GB
dc.titleThe role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.en_GB
dc.contributor.departmentRespiratory Research Division, Department of Medicine, Royal College of Surgeons , in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. , cmgreene@rcsi.ieen_GB
dc.identifier.journalExpert review of respiratory medicineen_GB
dc.description.provinceLeinster-

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