AJP - Lung AJP: Cell Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol (February 6, 2004). doi:10.1152/ajplung.00371.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
286/6/L1220    most recent
00371.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Panduri, V.
Right arrow Articles by Kamp, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Panduri, V.
Right arrow Articles by Kamp, D. W.
Submitted on October 30, 2003
Accepted on January 27, 2004

Mitochondrial-Derived Free Radicals Mediate Asbestos-Induced Alveolar Epithelial Cell Apoptosis

Vijayalakshmi Panduri1, Sigmund A. Weitzman2, Navdeep S. Chandel1, and David W. Kamp3*

1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
2 Department of Medicine, Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
3 Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; Veterans Administration Chicago Health Care System: Lakeside Division, Chicago, IL, USA

* To whom correspondence should be addressed. E-mail: d-kamp{at}northwestern.edu.

Asbestos causes pulmonary toxicity by mechanisms that in part involve reactive oxygen species (ROS). However, the precise source of ROS is unclear. We showed that asbestos induces alveolar epithelial cell (AEC) apoptosis by a mitochondria-regulated death pathway. To determine whether mitochondria-derived ROS are necessary for causing asbestos induced AEC apoptosis, we utilized A549 {rho}o cells that lack mitochondrial DNA and a functional electron transport. As expected, antimycin, which induces an oxidative stress by blocking mitochondrial electron transport at complex III, increased dichlorofluoroscein (DCF) fluorescence in A549 cells but not in A549 {rho}o cells. As compared to A549 cells, the {rho}o cells have less asbestosinduced ROS production as assessed by DCF fluorescence and reductions in total glutathione levels as well as less caspase 9 activation and apoptosis as assessed by TUNEL staining and DNA fragmentation. A mitochondrial anion channel inhibitor that prevents ROS release from the mitochondria to the cytoplasm also blocked asbestos-induced A549 cell caspase 9 activation and apoptosis. Finally, a role for non mitochondrial-derived ROS with exposure to high levels of asbestos (50 µg/cm2) was suggested by our findings that an iron chelator (phytic acid or deferoxamine) or a free radical scavenger (sodium benzoate) provided additional protection against asbestos-induced caspase 9 activation and DNA fragmentation in {rho}o cells. We conclude that asbestos fibers affect mitochondrial DNA and functional electron transport resulting in mitochondria-derived ROS production which in turn mediate AEC apoptosis. Nonmitochondrial associated ROS may also contribute to AEC apoptosis particularly with high levels of asbestos exposure.




This article has been cited by other articles:


Home page
 CarcinogenesisHome page
N. Azad, A. K. V. Iyer, A. Manosroi, L. Wang, and Y. Rojanasakul
Superoxide-mediated proteasomal degradation of Bcl-2 determines cell susceptibility to Cr(VI)-induced apoptosis
Carcinogenesis, August 1, 2008; 29(8): 1538 - 1545.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
D. J. Blake, C. M. Bolin, D. P. Cox, F. Cardozo-Pelaez, and J. C. Pfau
Internalization of Libby Amphibole Asbestos and Induction of Oxidative Stress in Murine Macrophages
Toxicol. Sci., September 1, 2007; 99(1): 277 - 288.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Soberanes, V. Panduri, G. M. Mutlu, A. Ghio, G. R. S. Bundinger, and D. W. Kamp
p53 Mediates Particulate Matter-induced Alveolar Epithelial Cell Mitochondria-regulated Apoptosis
Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1229 - 1238.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
V. Panduri, S. Surapureddi, S. Soberanes, S. A. Weitzman, N. Chandel, and D. W. Kamp
P53 Mediates Amosite Asbestos-Induced Alveolar Epithelial Cell Mitochondria-Regulated Apoptosis
Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 443 - 452.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Saito, J.-i. Ogawa, and Y. Minamiya
Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung
Am J Physiol Lung Cell Mol Physiol, September 1, 2005; 289(3): L400 - L406.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Upadhyay, V. Panduri, and D. W. Kamp
Fibroblast Growth Factor-10 Prevents Asbestos-Induced Alveolar Epithelial Cell Apoptosis by a Mitogen-Activated Protein Kinase-Dependent Mechanism
Am. J. Respir. Cell Mol. Biol., March 1, 2005; 32(3): 232 - 238.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
R. J. Tan, C. L. Fattman, S. C. Watkins, and T. D. Oury
Redistribution of pulmonary EC-SOD after exposure to asbestos
J Appl Physiol, November 1, 2004; 97(5): 2006 - 2013.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.