The DsbA-L gene is associated with respiratory function of the elderly via its adiponectin multimeric or antioxidant properties.
Aged
Aged, 80 and over
Alleles
Epithelial Cells
/ metabolism
Female
Forced Expiratory Volume
/ genetics
Gene Frequency
Gene Knockdown Techniques
Genotype
Glutathione Transferase
/ genetics
Humans
Male
Middle Aged
Oxidative Stress
/ genetics
Polymorphism, Single Nucleotide
Retrospective Studies
Vital Capacity
/ genetics
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 04 2020
06 04 2020
Historique:
received:
12
06
2019
accepted:
18
03
2020
entrez:
7
4
2020
pubmed:
7
4
2020
medline:
1
12
2020
Statut:
epublish
Résumé
Oxidative stress and inflammation play a key role in the age-related decline in the respiratory function. Adipokine in relation to the metabolic and inflammatory systems is attracting growing interest in the field of respiratory dysfunction. The present clinical and experimental studies investigated the role of the disulfide bond-forming oxidoreductase A-like protein (DsbA-L) gene, which has antioxidant and adiponectin multimeric (i.e. activation) properties, on the respiratory function of the elderly. We performed a retrospective longitudinal genotype-phenotype relationship analysis of 318 Japanese relatively elderly participants (mean age ± standard deviation: 67.0 ± 5.8 years) during a health screening program and an in vitro DsbA-L knock-down evaluation using 16HBE14o-cells, a commonly evaluated human airway epithelial cell line. The DsbA-L rs1917760 polymorphism was associated with a reduction in the ratio of forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and %FEV1 and with the elevation of the prevalence of FEV1/FVC < 70%. We also confirmed that the polymorphism was associated with a decreased respiratory function in relation to a decrease in the ratio of high-molecular-weight adiponectin/total adiponectin (as a marker of adiponectin multimerization) and an increase in the oxidized human serum albumin (as an oxidative stress marker). Furthermore, we clarified that DsbA-L knock-down induced oxidative stress and up-regulated the mucus production in human airway epithelial cells. These findings suggest that the DsbA-L gene may play a role in protecting the respiratory function of the elderly, possibly via increased systemic adiponectin functions secreted from adipocytes or through systemic and/or local pulmonary antioxidant properties.
Identifiants
pubmed: 32249844
doi: 10.1038/s41598-020-62872-5
pii: 10.1038/s41598-020-62872-5
pmc: PMC7136289
doi:
Substances chimiques
GSTK1 protein, human
EC 2.5.1.18
Glutathione Transferase
EC 2.5.1.18
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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