Antiinflammatory adaptation to hypoxia through adenosine-mediated cullin-1 deneddylation (JCI, 2007, 117:703-711)

報告日期: 2007/10/26
報告時間: 17:10/18:00
報告學生: 施惠瀅
講評老師: 黃朝慶

Antiinflammatory adaptation to hypoxia through adenosine-mediated cullin-1 deneddylation


J Clin Invest.  2007, 117, 703-11


Speaker: 施惠瀅                                   

Commentator: 黃朝慶老師         

Time: 17:10-18:00

Place: Room 602




Inflammation is a common phenomenon in many pulmonary disorders.  NF-kB is an important factor involving in many inflammatory disorders including hypoxia-induced pulmonary inflammation.  Hypoxia preconditioning (HPC), defined as a brief hypoxia treatment prior to the subsequent severe hypoxia insult, could increase cellular resistance to subsequent lethal hypoxia injury (1) though the undying mechanism remains unclear. In this study, the authors sought to define the anti-inflammatory properties of HPC.  The results showed that adenosine secreted by HPC-treated cells would inhibit IkBa  degradation thus suppressing NF-kB-mediated inflammation.  Treatment with adenosine analog N-ethyl-carbamido-adenosine (NECA) resulted in similar effect as that induced by HPC treatment.  Down regulation of CSN5 by siRNA inhibited NECA-induced cullin-1 deneddylation and resulted in a loss of protection by HPC as measured by NF-kB activity.  CD73-/- null mice, which lack the capability to produce adenosine, failed to exert HPC protective effect as compared with wild type.  Taken together, the result demonstrates an important role of adenosine, that is, adenosine is an anti-inflammatory molecule released in HPC.  The function of adenosine in HPC-mediated anti-inflammation is through blocking cullin-1 deneddylation thus inhibiting NF-kB transactivation.




1.       Zhang, J., Qian, H., Zhao, P., Hong, S.S., and Xia, Y. 2006.  Rapid hypoxia preconditioning protects cortical neurons from glutamate toxicity through delta-opioid receptor.  Stroke 37:1094-1099.