Proapoptotic Noxa is required for particulate matter-induced cell death and lung inflammation
AUTOR(ES)
Urich, Daniela
FONTE
The Federation of American Societies for Experimental Biology
RESUMO
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 (PM2.5) collected from the ambient air in Washington, D. C. Exposure to PM2.5 induced apoptosis in primary alveolar epithelial cells from wild-type but not Noxa−/− mice. Twenty-four hours after the intratracheal instillation of PM2.5, 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 PM2.5-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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2704586Documentos Relacionados
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