| Title: | Epithelial ablation of Bcl-XL increases sensitivity to oxygen without disrupting lung development |
| Author(s): | Staversky RJ; Vitiello PF; Yee M; Callahan LM; Dean DA; O'Reilly MA; |
| Address: | "Department of Pediatrics, University of Rochester, NY 14642, USA" |
| Journal Title: | Am J Respir Cell Mol Biol |
| ISSN/ISBN: | 1535-4989 (Electronic) 1044-1549 (Print) 1044-1549 (Linking) |
| Abstract: | "Recent studies indicate that the antiapoptotic Bcl-X(L), one of five isoforms expressed by the Bcl-X gene, protects a variety of cell lines exposed to hyperoxia. However, its role in lung development and protection against oxidative stress in vivo is not known. Here, we show Bcl-X(L) is the predominant isoform expressed in the lung, and the only isoform detected in respiratory epithelium. Because loss of Bcl-X(L) is embryonically lethal, Bcl-X(L) was ablated throughout the respiratory epithelium by mating mice with a floxed exon II of the Bcl-X gene with mice expressing Cre under control of the surfactant protein-C promoter. Interestingly, the loss of Bcl-X(L) in respiratory epithelium was perinatally lethal in approximately 50% of the expected offspring. However, some adult mice lacking the gene were obtained. The epithelial-specific ablation of Bcl-X(L) did not disrupt pulmonary function, the expression of epithelial cell-specific markers, or lung development. However, it shifted the lung toward a proapoptotic state, defined by a reduction in antiapoptotic Mcl-1, an increase in proapoptotic Bak, and increased sensitivity of the respiratory epithelium to hyperoxia. Intriguingly, increased 8-oxoguanine lesions seen during hyperoxia were also evident as lungs transitioned to room air at birth, a time when perinatal lethality in some mice lacking Bcl-X(L) was observed. These findings reveal that the epithelial-specific expression of Bcl-X(L) is not required for proper lung development, but functions to protect respiratory epithelial cells against oxygen-induced toxicity, such as during hyperoxia and the lung's first exposure to ambient air" |
| Keywords: | "Animals Apoptosis Blotting, Western Guanine/analogs & derivatives/metabolism Hyperoxia Integrases/metabolism Lung/growth & development/*metabolism Mice Mice, Knockout Oxygen/*metabolism RNA, Messenger/genetics Respiratory Mucosa/cytology/*metabolism Rever;" |
| Notes: | "MedlineStaversky, Rhonda J Vitiello, Peter F Yee, Min Callahan, Linda M Dean, David A O'Reilly, Michael A eng R01 EB009903-02/EB/NIBIB NIH HHS/ R01 HL067392/HL/NHLBI NIH HHS/ HL-091968/HL/NHLBI NIH HHS/ P30 ES001247/ES/NIEHS NIH HHS/ HL-67392/HL/NHLBI NIH HHS/ R01 HL081148/HL/NHLBI NIH HHS/ R21 HL092801-03/HL/NHLBI NIH HHS/ R01 HL081148-04/HL/NHLBI NIH HHS/ ES-01247/ES/NIEHS NIH HHS/ R01 HL059956/HL/NHLBI NIH HHS/ HL-59956/HL/NHLBI NIH HHS/ R01 HL059956-09/HL/NHLBI NIH HHS/ R21 HL092801/HL/NHLBI NIH HHS/ R01 EB009903/EB/NIBIB NIH HHS/ HL-81148/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2009/11/03 Am J Respir Cell Mol Biol. 2010 Sep; 43(3):376-85. doi: 10.1165/rcmb.2009-0165OC. Epub 2009 Oct 30" |
