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

doi:10.1165/rcmb.2002-0269OC

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

Medicine, Pulmonary Division

Research output: Contribution to journal › Article › peer-review

163 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 (Δψ_m), 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 Δψ_m 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 language	English (US)
Pages (from-to)	180-187
Number of pages	8
Journal	American journal of respiratory cell and molecular biology
Volume	29
Issue number	2
DOIs	https://doi.org/10.1165/rcmb.2002-0269OC
State	Published - Aug 1 2003

ASJC Scopus subject areas

Molecular Biology
Pulmonary and Respiratory Medicine
Clinical Biochemistry
Cell Biology

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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.",

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AB - 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.

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

Abstract

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