Sharabi Kfir, Hurwitz Anat, Simon Amos J, Beitel Greg J, Morimoto Richard I, Rechavi Gideon, Sznajder Jacob I, Gruenbaum Yosef
Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):4024-9. doi: 10.1073/pnas.0900309106. Epub 2009 Feb 23.
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.
高碳酸血症(二氧化碳水平升高)在多种肺部疾病中都会出现,并且与慢性阻塞性肺疾病(COPD)患者的不良预后相关。然而,在非神经元细胞中,高碳酸血症是如何被感知以及如何做出反应,在很大程度上尚不清楚。在此,我们利用秀丽隐杆线虫来研究其对非麻醉性二氧化碳水平的反应,并表明超过9%的二氧化碳水平会诱发异常运动,同时伴随着身体肌肉组织的年龄依赖性退化、发育迟缓、生育力下降和寿命延长。这些影响独立于胰岛素样生长因子受体(IGF-R)、饮食限制、产卵或线粒体诱导的衰老途径而发生。转录谱分析显示,在暴露于19%二氧化碳1、6或72小时后,基因表达发生了特定的动态变化,包括几个7跨膜结构域基因和先天免疫基因的转录增加,以及许多MSP基因的转录减少。总之,这些结果表明了对高碳酸血症的特定生理和分子反应,这些反应似乎独立于早期热休克和缺氧诱导因子(HIF)介导的途径。