The relationship between DJ-1 and S100A8 in human primary alveolar type II cells in emphysema

Chih Ru Lin, Karim Bahmed, Dhanendra Tomar, Nathaniel Marchetti, Gerard J. Criner, Sudhir Bolla, Mark A. Wilson, Muniswamy Madesh, Beata Kosmider

Research output: Contribution to journalArticle

Abstract

Pulmonary emphysema is characterized by alveolar type II (ATII) cell death, destruction of alveolar wall septa, and irreversible airflow limitation. Cigarette smoke induces oxidative stress and is the main risk factor for this disease development. ATII cells isolated from nonsmokers, smokers, and patients with emphysema were used for this study. ATII cell apoptosis in individuals with this disease was detected. DJ-1 and S100A8 have cytoprotective functions against oxidative stress-induced cell injury. Reduced DJ-1 and S100A8 interaction was found in ATII cells in patients with emphysema. The molecular function of S100A8 was determined by an analysis of the oxidation status of its cysteine residues using chemoselective probes. Decreased S100A8 sulfination was observed in emphysema patients. In addition, its lower levels correlated with higher cell apoptosis induced by cigarette smoke extract in vitro. Cysteine at position 106 within DJ-1 is a central redox-sensitive residue. DJ-1 C106A mutant construct abolished the cytoprotective activity of DJ-1 against cell injury induced by cigarette smoke extract. Furthermore, a molecular and complementary relationship between DJ-1 and S100A8 was detected using gain- and loss-of-function studies. DJ-1 knockdown sensitized cells to apoptosis induced by cigarette smoke extract, and S100A8 overexpression provided cytoprotection in the absence of DJ-1. DJ-1 knockout mice were more susceptible to ATII cell apoptosis induced by cigarette smoke compared with wild-type mice. Our results indicate that the impairment of DJ-1 and S100A8 function may contribute to cigarette smoke-induced ATII cell injury and emphysema pathogenesis.

Original languageEnglish (US)
Pages (from-to)L791-L804
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume317
Issue number6
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

  • Alveolar type II cells
  • Cigarette smoke
  • DJ-1
  • Emphysema
  • S100A8

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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