HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-114546v1 fj.08-114546v2 23/7/2055    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Urich, D. Articles by Budinger, G. R. S. Search for Related Content PubMed PubMed Citation Articles by Urich, D. Articles by Budinger, G. R. S.

Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation

Daniela Urich^*,1, Saul Soberanes^*,1, Zach Burgess^*, Sergio E. Chiarella^*, Andrew J. Ghio, Karen M. Ridge^*, David W. Kamp^*, Navdeep S. Chandel^*, Gökhan M. Mutlu^* and G. R. Scott Budinger^*,2

^* Division of Pulmonary and Critical Care Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; and

U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA

² Correspondence: Northwestern University, Division of Pulmonary and Critical Care Medicine, 240 E. Huron, McGaw Pavilion M300, Chicago, IL 60611, USA. E-mail: s-buding{at}northwestern.edu

Elevated ambient levels of particulate matter air pollution are associated with excess daily mortality, largely attributable to increased rates of cardiovascular events. We have previously reported that particulate matter induces p53-dependent apoptosis in primary human alveolar epithelial cells. Activation of the intrinsic apoptotic pathway by p53 often requires the transcription of the proapoptotic Bcl-2 proteins Noxa, Puma, or both. In this study, we exposed alveolar epithelial cells in culture and mice to fine particulate matter <2.5 µm in diameter (PM_2.5) collected from the ambient air in Washington, D. C. Exposure to PM_2.5 induced apoptosis in primary alveolar epithelial cells from wild-type but not Noxa^–/– mice. Twenty-four hours after the intratracheal instillation of PM_2.5, wild-type mice showed increased apoptosis in the lung and increased levels of mRNA encoding Noxa but not Puma. These changes were associated with increased permeability of the alveolar-capillary membrane and inflammation. All of these findings were absent or attenuated in Noxa^–/– animals. We conclude that PM_2.5-induced cell death requires Noxa both in vitro and in vivo and that Noxa-dependent cell death might contribute to PM-induced alveolar epithelial dysfunction and the resulting inflammatory response.—Urich, D., Soberanes, S., Burgess, Z., Chiarella, S. E., Ghio, A. J., Ridge, K. M., Kamp, D. W., Chandel, N. S., Mutlu, G. M., Budinger, G. R. S. Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation.

Key Words: apoptosis • oxidant • bax • air pollution

This article has been cited by other articles:

				V. C. Van Hee, J. D. Kaufman, G. R. S. Budinger, and G. M. Mutlu Update in Environmental and Occupational Medicine 2009 Am. J. Respir. Crit. Care Med., June 1, 2010; 181(11): 1174 - 1180. [Full Text] [PDF]