Redox signaling-mediated S-glutathionylation of protein disulfide isomerase A1 initiates intrinsic apoptosis and contributes to accelerated aging.

ABSTRACT: Identifying factors that contribute to the age-related onset of chronic obstructive pulmonary disease (COPD) is crucial for its prevention and treatment. The multifunctional endoplasmic reticulum (ER) chaperone protein disulfide isomerase A1 (PDIA1) shows a protective increase in expression levels in human and mouse non-COPD smokers. However, this increase slows with aging and disease progression, while increase in glutathione S-transferase π1 (GSTP1) does not. PDI has redox sensitive cysteine residues that can become S-glutathionylated (PDI-SSG) which compromise both isomerase and chaperone activity. Oxidized PDIA1 levels progressively rise with age in the lungs of murine non-smokers, with an even greater increase in smokers. To investigate whether an increased oxidized-to-native PDIA1 ra

SUBMITTER: Ye ZW 

PROVIDER: S-EPMC12172305 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature