Particulate matter induces alveolar epithelial cell DNA damage and apoptosis role of free radicals and the mitochondria

Daya Upadhyay, Vijayalakshmi Panduri, Andrew Ghio, David W. Kamp*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Airborne particulate matter (PM) increases morbidity and mortality resulting from cardiopulmonary diseases including cancer. We hypothesized that PM is genotoxic to alveolar epithelial cells (AEC) by causing DNA damage and apoptosis. PM caused dose-dependent AEC DNA strand break formation, reductions in mitochondrial membrane potential (Δψm), caspase 9 activation, and apoptosis. An iron chelator and a free radical scavenger prevented these effects. Finally, overexpression of Bcl-xl, a mitochondrial anti-apoptotic protein, blocked PM-induced Δψm and DNA fragmentation. We conclude that PM causes AEC DNA damage and apoptosis by mechanisms that involve the mitochondria-regulated death pathway and the generation of iron-derived free radicals.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume29
Issue number2
DOIs
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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