| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,2
* Department of Pharmacology and Toxicology and
Department of Anesthesiology and Intensive Care Medicine and
Department of Pathology, Tübingen University Hospital, Tübingen, Germany;
Pharmaceutical Institute, University of Bonn, Bonn, Germany; and
|| Liver and Transplant Centers, Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
2Correspondence: H.K.E., Department of Anesthesiology and Intensive Care Medicine, Tübingen University Hospital, Zentrum für Medizinische Forschung, Waldhörnle Str. 22, D-72072 Tübingen, Germany; E-mail: heltzschig{at}partners.org or H.O., Department of Pharmacology and Toxicology, Tübingen University Hospital, Wilhelmstr. 56, D-72074 Tübingen, Germany; E-mail: hartmut.osswald{at}uni-tuebingen.de
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-diphosphohydrolases (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-NTPDase1–3, 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., Müller, C. E., Robson, S. C., Osswald, H., Eltzschig, H. K. Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury.
Key Words: acute renal failure • kidney • preconditioning • NTPDase
This article has been cited by other articles:
|
|
 |
|
  M. Oppermann, D. J. Friedman, R. Faulhaber-Walter, D. Mizel, H. Castrop, K. Enjyoji, S. C. Robson, and J. Schnermann Tubuloglomerular feedback and renin secretion in NTPDase1/CD39-deficient mice Am J Physiol Renal Physiol, April 1, 2008; 294(4): F965 - F970. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Eckle, M. Faigle, A. Grenz, S. Laucher, L. F. Thompson, and H. K. Eltzschig A2B adenosine receptor dampens hypoxia-induced vascular leak Blood, February 15, 2008; 111(4): 2024 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Joo, M. Kim, P. Horst, J. Kim, V. D. D'Agati, C. W. Emala Sr., and H. T. Lee Acute and delayed renal protection against renal ischemia and reperfusion injury with A1 adenosine receptors Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1847 - F1857. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
