The role of DJ-1 in human primary alveolar type II cell injury induced by e-cigarette aerosol

Karim Bahmed, Chih Ru Lin, Hannah Simborio, Loukmane Karim, Mark Aksoy, Steven Kelsen, Dhanendra Tomar, Muniswamy Madesh, John Elrod, Elise Messier, Robert Mason, Ellen M. Unterwald, Toby K. Eisenstein, Gerard J. Criner, Beata Kosmider

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

The alveolus participates in gas exchange, which can be impaired by environmental factors and toxins. There is an increase in using electronic cigarettes (e-cigarettes); however, their effect on human primary alveolar epithelial cells is unknown. Human lungs were obtained from nonsmoker organ donors to isolate alveolar type II (ATII) cells. ATII cells produce and secrete pulmonary surfactant and restore the epithelium after damage, and mitochondrial function is important for their metabolism. Our data indicate that human ATII cell exposure to e-cigarette aerosol increased IL-8 levels and induced DNA damage and apoptosis. We also studied the cytoprotective effect of DJ-1 against ATII cell injury. DJ-1 knockdown in human primary ATII cells sensitized cells to mitochondrial dysfunction as detected by high mitochondrial superoxide production, decreased mitochondrial membrane potential, and calcium elevation. DJ-1 knockout (KO) mice were more susceptible to ATII cell apoptosis and lung injury induced by e-cigarette aerosol compared with wild-type mice. Regulation of the oxidative phosphorylation (OXPHOS) is important for mitochondrial function and protection against oxidative stress. Major subunits of the OXPHOS system are encoded by both nuclear and mitochondrial DNA. We found dysregulation of OXPHOS complexes in DJ-1 KO mice after exposure to e-cigarette aerosol, which could disrupt the nuclear/mitochondrial stoichiometry, resulting in mitochondrial dysfunction. Together, our results indicate that DJ-1 deficiency sensitizes ATII cells to damage induced by e-cigarette aerosol leading to lung injury.

Original languageEnglish (US)
Pages (from-to)L475-L485
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Volume317
Issue number4
DOIs
StatePublished - Oct 1 2019
Externally publishedYes

Keywords

  • DJ-1
  • alveolar type II cells
  • e-cigarette aerosol
  • lung
  • mitochondria

ASJC Scopus subject areas

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

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