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Contribution of E‐NTPDasel (CD39) to renal protection from ischemia‐reperfusion injury
Author(s) -
Grenz Almut,
Zhang Hua,
Hermes Marina,
Eckle Tobias,
Klingel Karin,
Huang Dan Yang,
Müller Christa E.,
Robson Simon C.,
Osswald Hartmut,
Eltzschig Holger K.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-7947com
Subject(s) - apyrase , adenosine , kidney , ischemia , renal ischemia , pharmacology , medicine , extracellular , nucleoside , purinergic signalling , chemistry , reperfusion injury , biochemistry , adenosine receptor , receptor , agonist
Previous studies showed increased extracellular nucleotides during renal ischemia‐reperfusion. While nucleotides represent the main source for extracellular adenosine and adenosine signaling contributes to renal protection from ischemia, we hypothesized a role for ecto‐nucleoside‐triphosphate‐diphosphohydro‐lases (E‐NTPDases) in renal protection. We used a model of murine ischemia‐reperfusion and in situ ischemic preconditioning (IP) via a hanging weight system for atraumatic renal artery occlusion. Initial studies with a nonspecific inhibitor of E‐NTPDases (POM‐1) revealed inhibition of renal protection by IP. We next pursued transcriptional responses of E‐NTPDases (E‐NTPDasel‐3, and 8) to renal IP, and found a robust and selective induction of E‐NTPDase1/CD39 transcript and protein. Moreover, based on clearance studies, plasma electrolytes, and renal tubular histology, IP protection was abolished in gene‐targeted mice for cd39 whereas increased renal adenosine content with IP was attenuated. Furthermore, administration of apyrase reconstituted renal protection by IP in cd39 −/− mice. Finally, apyrase treatment of wild‐type mice resulted in increased renal adenosine concentrations and a similar degree of renal protection from ischemia as IP treatment. Taken together, these data identify CD39‐dependent nucleotide phosphohydrolysis in renal protection. Moreover, the present studies suggest apyrase treatment as a novel pharmacological approach to renal diseases precipitated by limited oxygen availability.—Grenz, A., Zhang, H., Hermes, M., Eckle, T., Klingel, K., Huang, D. Y., Muller, C. E., Robson, S. C., Osswald, H., Eltzschig, H. K. Contribution of E‐NTPDasel (CD39) to renal protection from ischemia‐reperfusion injury. FASEB J. 21, 2863–2873 (2007)