Yuanyuan Cheng and Jianhui Rong* Pages 3884 - 3898 ( 15 )
Background: Ischemia-reperfusion (I/R) injury causes the dysfunctions of different major organs, leading to morbidity and mortality on the global scale. Among a battery of therapeutic targets, the heme oxygenase- 1 (HO-1)/carbon monoxide (CO) system has been evaluated for the development of new therapies against I/R injury. The enzyme HO-1 catalyzes the degradation of heme into three biologically active end products, namely biliverdin/bilirubin, CO and ferrous ion. Interestingly, CO is one of a few bioactive gaseous molecules with the capability of regulating inflammation, cell survival and growth. In fact, several CO-releasing compounds have been developed for directly reprogramming the intracellular apoptotic, inflammatory and proliferative signaling networks. In parallel, chemical and genetic approaches have also been evaluated for up-regulating HO-1 expression as an endogenous mechanism to ameliorate I/R injury and heal wounds.
Methods: In this review, we discussed the recent studies on the therapeutic potential of HO-1/CO system in the treatment of I/R injury in the heart, brain, liver, kidney, lung, intestine and retina. We focused on the activities and underlying mechanisms of various therapeutic strategies to regulate HO-1/CO system against I/R injury.
Results: A large number of studies have demonstrated that HO-1/CO system exhibits potent anti-oxidative, antiapoptotic, anti-inflammatory and cytoprotective activities against I/R injury. The regulation of HO-1/CO expression has been achieved either by genetic overexpression of HO-1 cDNA or pharmacological induction with drugs including curcumin and resveratrol.
Conclusion: The HO-1/CO system is a potential target for treating I/R injury. Further studies should be directed to in vivo efficacy and clinical application of HO-1/CO system in the therapy of I/R injury.
Ischemia-reperfusion injury, hemo oxygenase-1/carbon monoxide, anti-oxidative, anti-apoptotic, anti-inflammatory, pharmacological induction.
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, P.O. Box: 0000-000, Hong Kong