AMP deaminase 3 plays a critical role in remote reperfusion lung injury.

Abstract

Remote reperfusion lung injury following skeletal muscle ischemia and reperfusion accounts for high morbidity and mortality. AMP deaminase (AMPD), a key enzyme for nucleotide cycle, has been implicated in the regulation of this phenomenon. However, the function of Ampd2 and Ampd3 subtype has not been elucidated in remote reperfusion rodent lung injury. We utilized AMPD3 and AMPD2-deficient mice. The two types of AMPD-deficient mice and wild-type (WT) littermates were subjected to ischemia-reperfusion injury. After 3h bilateral hind-limb ischemia and reperfusion, AMPD3 mRNA, AMPD activity and inosine monophosphate (IMP) increased significantly in WT and AMPD2-deficient mice lungs, while they did not show significant alterations in AMPD3-deficient mice lungs. Genetic inactivation of Ampd3 resulted in markedly accelerated myeloperoxidase (MPO) activity along with exaggerated neutrophils infiltration and hemorrhage in the lungs compared to WT and AMPD2-deficient mice, furthermore, IMP treatment significantly attenuated MPO activity and neutrophils infiltration in WT and the two types of AMPD-deficient mice lungs after 3h reperfusion. These findings demonstrate for the first time in AMP-deficient mice models that AMPD3 plays a critical role in remote reperfusion lung injury via generation of IMP and validate the potential to use IMP into the clinical arena to attenuate remote ischemia-reperfusion lung injury.

• Authors: Peili Li, Kazuhide Ogino, Yoshiko Hoshikawa, Hiroko Morisaki, Keiko Toyama, Takayuki Morisaki, Kumi Morikawa, Haruaki Ninomiya, Akio Yoshida, Kiyoshi Hashimoto, Yasuaki Shirayoshi, Ichiro Hisatome
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 434 Issue 1 Pg. 131-6 (Apr 26 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23542464 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Inosine Monophosphate
• AMP Deaminase
• AMPD3 protein, mouse

Topics

• AMP Deaminase (deficiency, genetics, physiology)
• Animals
• Disease Models, Animal
• Inosine Monophosphate (administration & dosage, biosynthesis)
• Lung Injury (enzymology, genetics, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Reperfusion Injury (enzymology, genetics, pathology)