Hypoxia, which is defined as a shortage of oxygen, can occur throughout the body (e.g., at high altitude) or within a specific organ or tissue of the body (e.g., due to blockage of a blood vessel, which in the heart ultimately results in a heart attack). In many instances, inflammation is the response of the body to hypoxia and this often causes many of the problems that arise from hypoxia. However, the body can be protected from some of the more severe effects of hypoxia by hypoxic preconditioning (HPC), i.e., exposure to moderately decreased amounts of oxygen.
In a study that appears online in advance of publication in the March print issue of the Journal of Clinical Investigation, Juan Ibla and colleagues from Children's Hospital Boston, show that if mice undergo HPC their lungs exhibit an attenuated inflammatory response to severe hypoxia compared with mice that received no HPC. In particular, the expression of genes regulated by the pro-inflammatory regulator NF-kappa-B was decreased. This decrease in NF-kappa-B activation was mediated by adenosine produced by cells exposed to HPC. Further analysis showed that adenosine inactivated a protein (cullin-1) that is required for NF-kappa-B activation by a process known as deneddylation. This study identifies an anti-inflammatory mechanism activated in the lungs by HPC and mediated by adensosine. Future studies will investigate whether the same mechanism protects other tissues from the severe effects of hypoxia.
TITLE: Antiinflammatory adaptation to hypoxia through adenosine-mediated cullin-1 deneddylation
AUTHOR CONTACT:
Juan C. Ibla
Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
JCI table of contents -- February 22, 2006
Contact: Karen Honey
Journal of Clinical Investigation
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