| Extracellular adenosine production by ecto-5'-nucleotidase protects during murine hepatic ischemic preconditioning. | |
| | |
MedLine Citation:
|
PMID: 18804111 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND & AIMS: The liver tolerates ischemia/reperfusion (IR) poorly. The discovery of ischemic preconditioning (IP) has raised hopes that natural pathways could be activated to increase hepatic resistance to ischemia. However, mechanisms of hepatic IP remain largely unknown. Extracellular adenosine has been implicated as an innate anti-inflammatory metabolite, particularly during ischemia. We investigated whether ecto-5'-nucleotidase (CD73), the "pacemaker" enzyme of extracellular adenosine production, is critical for hepatic protection by IP. METHODS: Mice were subjected to 4 cycles of portal triad occlusion and reperfusion (3 minutes of ischemia/3 minutes of reperfusion) prior to IR or IR alone. RESULTS: Hepatic IP was associated with a significant induction of CD73 transcript and protein. Targeted gene deletion or pharmacologic inhibition of CD73 abolished hepatic protection by IP as measured by lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase serum levels or histologic injury. Increases in extracellular adenosine with IP were significantly attenuated in cd73-deficient (cd73(-/-)) mice. Reconstitution of cd73(-/-) mice with soluble 5'-nucleotidase resulted in complete restoration of hepatoprotection by IP, and hepatic injury following ischemia was attenuated by treatment of WT mice with soluble 5'-nucleotidase. Mice deficient in CD73 did not demonstrate the same degree of IP-dependent inhibition of acute phase complement gene expression/activation as did wild-type mice suggesting that extracellular adenosine attenuates hepatic IR via complement regulation. CONCLUSIONS: Extracellular adenosine production by CD73 mediates protection during murine hepatic IP. Use of soluble 5'-nucleotidase may be a potential therapeutic for hepatic ischemia. |
| | |
Authors:
|
Melanie L Hart; Chressen Much; Iris C Gorzolla; Jens Schittenhelm; Doris Kloor; Gregory L Stahl; Holger K Eltzschig |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-08-03 |
Journal Detail:
|
Title: Gastroenterology Volume: 135 ISSN: 1528-0012 ISO Abbreviation: Gastroenterology Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-11-10 Completed Date: 2008-11-25 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0374630 Medline TA: Gastroenterology Country: United States |
Other Details:
|
Languages: eng Pagination: 1739-1750.e3 Citation Subset: AIM; IM |
Affiliation:
|
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
5'-Nucleotidase
/
genetics*,
metabolism Adenosine / biosynthesis* Animals Blotting, Western Disease Models, Animal Extracellular Fluid / enzymology Ischemic Preconditioning / methods* Liver / blood supply*, metabolism, pathology Mice RNA / genetics* Reperfusion Injury / complications, enzymology, prevention & control* Reverse Transcriptase Polymerase Chain Reaction Transcription, Genetic* |
| Grant Support | |
ID/Acronym/Agency:
|
DE16191/DE/NIDCR NIH HHS; DE17821/DE/NIDCR NIH HHS; DK067782/DK/NIDDK NIH HHS; HL52886/HL/NHLBI NIH HHS; HL56086/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
58-61-7/Adenosine; 63231-63-0/RNA; EC 3.1.3.5/5'-Nucleotidase |
| Comments/Corrections | |
Comment In:
|
Gastroenterology. 2008 Nov;135(5):1460-2
[PMID:
18848549
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sargaquinoic acid and sargahydroquinoic acid from Sargassum yezoense stimulate adipocyte differentia...
Next Document: Intestinal differentiation in zebrafish requires Cdx1b, a functional equivalent of mammalian Cdx2.