Citation:
Abstract:
Hypercapnia (high CO(2) levels) occurs in a number of lung diseases and it is associated with worse outcomes in patients with chronic obstructive lung disease (COPD). However, it is largely unknown how hypercapnia is sensed and responds in nonneuronal cells. Here, we used C. elegans to study the response to nonanesthetic CO(2) levels and show that levels exceeding 9% induce aberrant motility that is accompanied by age-dependent deterioration of body muscle organization, slowed development, reduced fertility and increased life span. These effects occur independently of the IGF-R, dietary restriction, egg laying or mitochondrial-induced aging pathways. Transcriptional profiling analysis shows specific and dynamic changes in gene expression after 1, 6, or 72 h of exposure to 19% CO(2) including increased transcription of several 7-transmembrane domain and innate immunity genes and a reduction in transcription of many of the MSP genes. Together, these results suggest specific physiological and molecular responses to hypercapnia, which appear to be independent of early heat shock and HIF mediated pathways.
Notes:
Sharabi, KfirHurwitz, AnatSimon, Amos JBeitel, Greg JMorimoto, Richard IRechavi, GideonSznajder, Jacob IGruenbaum, YosefengHL085534/HL/NHLBI NIH HHS/R01 GM069540/GM/NIGMS NIH HHS/GM069540/GM/NIGMS NIH HHS/R01 HL085534/HL/NHLBI NIH HHS/R01 AG026647/AG/NIA NIH HHS/Research Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tProc Natl Acad Sci U S A. 2009 Mar 10;106(10):4024-9. doi: 10.1073/pnas.0900309106. Epub 2009 Feb 23.